MHRA Drug Safety Update (June 2021): Atezolizumab (Tecentriq) and other immune-stimulatory anti-cancer drugs: risk of severe cutaneous adverse reactions (SCARs).

• Cases of severe cutaneous adverse reactions, including Stevens-Johnsons syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in patients treated with immune-stimulatory anti-cancer drugs
• Other products used for cancers in the same class as atezolizumab, including cemiplimab, ipilimumab, nivolumab, and pembrolizumab list SCARs (including SJS and TEN) as a possible side effect in the Summary of Product Characteristics (SmPC) with an associated warning and precautions. Avelumab and durvalumab are known to cause other immune-mediated skin adverse reactions
• Advise patients to be vigilant for the signs of severe skin reactions and to seek urgent medical advice if they occur

Anti-CTLA-4 monoclonal antibodies

Ipilimumab

• Solution for infusion vials 50mg/10ml, 200mg/40ml

Notes

1. NICE TA268: Ipilimumab (Yervoy) is recommended as an option for treating advanced (unresectable or metastatic) melanoma in people who have received prior therapy, only if the manufacturer provides ipilimumab with the discount agreed in the patient access scheme (December 2012).
2. NICE TA319: Ipilimumab is recommended as an option for treating adults with previously untreated advanced (unresectable or metastatic) melanoma, only if the manufacturer provides ipilimumab with the discount agreed in the patient access scheme (July 2014).
3. NICE TA400: Nivolumab (Opdivo) in combination with ipilimumab (Yervoy) is recommended as an option for treating advanced (unresectable or metastatic) melanoma in adults, only when the company provides ipilimumab with the discount agreed in the patient access scheme (July 2016).
4. NICE TA716: Nivolumab (Opdivo) plus ipilimumab (Yervoy) is recommended, within its marketing authorisation, as an option for treating metastatic colorectal cancer with high microsatellite instability (MSI) or mismatch repair (MMR) deficiency after fluoropyrimidine-based combination chemotherapy. It is recommended only if the company provides nivolumab and ipilimumab according to the commercial arrangement (July 2021).
5. NICE TA724: Nivolumab plus ipilimumab (Yervoy) and 2 cycles of platinum-doublet chemotherapy is not recommended, within its marketing authorisation, for untreated metastatic non-small-cell lung cancer (NSCLC) in adults whose tumours have no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations (September 2021).
6. NICE TA780: Nivolumab (Opdivo) with ipilimumab is recommended, within its marketing authorisation, as an option for untreated advanced renal cell carcinoma in adults (March 2022):
   1. whose disease is intermediate or poor risk as defined in the International Metastatic Renal Cell Carcinoma Database Consortium criteria and
   2. only if the company provides nivolumab with ipilimumab according to the commercial arrangement.
7. NICE TA818: Nivolumab (Opdivo) with ipilimumab (Yervoy) is recommended as an option for untreated unresectable malignant pleural mesothelioma in adults (August 2022), only if:
   1. they have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
   2. the company provides it according to the commercial agreement.
8. MHRA Drug Safety Update (July 2017): Nivolumab (Opdivo), pembrolizumab (Keytruda): reports of organ transplant rejection - Ipilimumab (Yervoy) may also interfere with immunosuppressive therapy, increasing the risk of graft rejection.
9. MHRA Drug Safety Update (January 2019): Ipilimumab (Yervoy): reports of cytomegalovirus (CMV) gastrointestinal infection or reactivation.
10. MHRA Drug Safety Update (June 2021): Atezolizumab (Tecentriq) and other immune-stimulatory anti-cancer drugs: risk of severe cutaneous adverse reactions (SCARs) - for more information see update summary at the top of the page.

Anti-PD-1 monoclonal antibodies

Atezolizumab

• Solution for infusion vials 1.2g/20ml, 840mg/14ml

Notes

1. NICE TA520: Atezolizumab (Tecentriq) is recommended as an option for treating locally advanced or metastatic non-small-cell lung cancer (NSCLC) in adults who have had chemotherapy (and targeted treatment if they have an EGFR- or ALK-positive tumour), only when the criteria of the NICE TA are met (May 2018).
2. NICE TA525: Atezolizumab (Tecentriq) is recommended as an option for treating locally advanced or metastatic urothelial carcinoma in adults who have had platinum-containing chemotherapy, only when the criteria of the NICE TA are met (June 2018).
3. NICE TA584: Atezolizumab (Tecentriq) plus bevacizumab (Avastin), carboplatin and paclitaxel is recommended as an option for metastatic non-squamous non-small-cell lung cancer (NSCLC) only when the criteria of the NICE TA are met (June 2019).
4. NICE TA638: Atezolizumab (Tecentriq) with carboplatin and etoposide is recommended as an option for untreated extensive-stage small-cell lung cancer in adults, only when the criteria of the NICE TA are met (July 2020).
5. NICE TA639: Atezolizumab (Tecentriq) with nab‑paclitaxel is recommended, within its marketing authorisation, for treating triple-negative, unresectable, locally advanced or metastatic breast cancer in adults whose tumours express PD‑L1 at a level of 1% or more and who have not had previous chemotherapy for metastatic disease. It is recommended only if the company provides atezolizumab according to the commercial arrangement (July 2020).
6. NICE TA666: Atezolizumab (Tecentriq) plus bevacizumab (Avastin) is recommended as an option for treating advanced or unresectable hepatocellular carcinoma (HCC) in adults who have not had previous systemic treatment (December 2020), only if:
   1. they have Child‑Pugh grade A liver impairment and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and
   2. the company provides it according to the commercial arrangement.
7. NICE TA705: Atezolizumab (Tecentriq) is recommended, within its marketing authorisation, as an option for untreated metastatic non-small-cell lung cancer (NSCLC) in adults (June 2021) if:
   1. their tumours have PD-L1 expression on at least 50% of tumour cells or 10% of tumour-infiltrating immune cells
   2. their tumours do not have epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations and
   3. the company provides atezolizumab according to the commercial arrangement.
8. NICE TA739: Atezolizumab (Tecentriq) is recommended, within its marketing authorisation, as an option for untreated locally advanced or metastatic urothelial cancer in adults whose tumours express PD‑L1 at a level of 5% or more and when cisplatin-containing chemotherapy is unsuitable (October 2021)
   1. This is only if the company provides atezolizumab according to the commercial arrangement.
9. NICE TA823: Atezolizumab (Tecentriq) is recommended for use within the Cancer Drugs Fund as an option for adjuvant treatment after complete tumour resection in adults with stage 2 to 3a non-small-cell lung cancer (NSCLC) (September 2022) whose:
   1. tumours have the programmed cell death ligand-1 (PD-L1) biomarker expression on 50% or more of their tumour cells and
   2. whose disease has not progressed after platinum-based adjuvant chemotherapy and
   3. the company provides atezolizumab according to the managed access agreement.
10. MHRA Drug Safety Update (June 2021): Atezolizumab (Tecentriq) and other immune-stimulatory anti-cancer drugs: risk of severe cutaneous adverse reactions (SCARs) - for more information see update summary at the top of the page.

Avelumab

• Solution for infusion vials 200mg/10ml

Notes

1. NICE TA517: Avelumab (Bavencio) is recommended as an option for treating metastatic Merkel cell carcinoma in adults, only if they have had 1 or more lines of chemotherapy for metastatic disease. It is recommended only if the company provides avelumab according to the commercial arrangement (April 2018).
2. NICE TA691: Avelumab (Bavencio) is recommended as an option for treating metastatic Merkel cell carcinoma in adults who have not had chemotherapy for metastatic disease. It is recommended only if the company provides avelumab according to the commercial arrangement (April 2021).
3. NICE TA645: Avelumab (Bavencio) with axitinib (Inlyta) is recommended for use within the Cancer Drugs Fund as an option for untreated advanced renal cell carcinoma in adults. It is recommended only if the conditions in the managed access agreement for avelumab with axitinib are followed (September 2020).
4. NICE TA788: Avelumab (Bavencio) is recommended as an option for maintenance treatment of locally advanced or metastatic urothelial cancer that has not progressed after platinum-based chemotherapy in adults (May 2022), only if:
   1. avelumab is stopped at 5 years of uninterrupted treatment or earlier if the disease progresses and
   2. the company provides avelumab according to the commercial arrangement.
5. MHRA Drug Safety Update (June 2021): Atezolizumab (Tecentriq) and other immune-stimulatory anti-cancer drugs: risk of severe cutaneous adverse reactions (SCARs) - for more information see update summary at the top of the page.

Cemiplimab

• Solution for infusion vials 350mg/7ml

Notes

1. NICE TA802: Cemiplimab (Libtayo) is recommended as an option for treating metastatic or locally advanced cutaneous squamous cell carcinoma in adults when curative surgery or curative radiotherapy is not suitable (June 2022), only if:
   1. it is stopped at 24 months, or earlier if their disease progresses, and
   2. the company provides it according to the commercial arrangement.
2. MHRA Drug Safety Update (June 2021): Atezolizumab (Tecentriq) and other immune-stimulatory anti-cancer drugs: risk of severe cutaneous adverse reactions (SCARs) - for more information see update summary at the top of the page.

Dostarlimab

• Solution for infusion vials 500mg/10ml

Notes

1. NICE TA779: Dostarlimab (Jemperli) is recommended for use within the Cancer Drugs Fund as an option for treating advanced or recurrent endometrial cancer with high microsatellite instability or mismatch repair deficiency in adults who have had platinum-based chemotherapy, only if the conditions in the managed access agreement are followed (March 2022).
2. NICE TA963: Dostarlimab (Jemperli) with platinum-based chemotherapy is recommended with managed access as an option for treating primary advanced or recurrent endometrial cancer with high microsatellite instability or mismatch repair deficiency in adults who are candidates for systemic therapy, only if the conditions in the managed access scheme are followed (April 2024).

Durvalumab

• Solution for infusion vials 120mg/2.4ml, 500mg/10ml

Notes

1. NICE TA798: Durvalumab (Imfinzi) is recommended as an option for treating locally advanced unresectable non-small-cell lung cancer (NSCLC) in adults whose tumours express programmed cell death ligand 1 (PD-L1) on 1% or more of cells and whose disease has not progressed after platinum-based chemoradiation (June 2022), only if:
   1. they have had concurrent platinum-based chemoradiation
   2. the company provides durvalumab according to the commercial arrangement.
2. NICE TA944: Durvalumab (Imfinzi) plus gemcitabine and cisplatin is recommended, within its marketing authorisation, as an option for treating locally advanced, unresectable, or metastatic biliary tract cancer in adults, only if the company provides durvalumab according to the commercial arrangement (January 2024).
3. MHRA Drug Safety Update (June 2021): Atezolizumab (Tecentriq) and other immune-stimulatory anti-cancer drugs: risk of severe cutaneous adverse reactions (SCARs) - for more information see update summary at the top of the page.

Nivolumab

• Solution for infusion vials 40mg/4ml, 100mg/10ml, 120mg/12ml, 240mg/24ml

Notes

1. NICE TA384: Nivolumab (Opdivo) is recommended as an option for treating advanced (unresectable or metastatic) melanoma in adults (February 2016).
2. NICE TA400: Nivolumab (Opdivo) is recommended, in combination with ipilimumab (Yervoy), as an option for treating advanced (unresectable or metastatic) melanoma, only when the company provides ipilimumab with the discount agreed in the patient access scheme (July 2016).
3. NICE TA684: Nivolumab (Opdivo) is recommended, within its marketing authorisation, as an option for the adjuvant treatment of completely resected melanoma in adults with lymph node involvement or metastatic disease. It is recommended only if the company provides nivolumab according to the commercial arrangement (March 2021).
4. NICE TA417: Nivolumab (Opdivo) is recommended as an option for previously treated advanced renal cell carcinoma in adults, when the company provides nivolumab according to the commercial arrangement (November 2016).
5. NICE TA780: Nivolumab (Opdivo) with ipilimumab is recommended, within its marketing authorisation, as an option for untreated advanced renal cell carcinoma in adults:
   1. whose disease is intermediate or poor risk as defined in the International Metastatic Renal Cell Carcinoma Database Consortium criteria and
   2. only if the company provides nivolumab with ipilimumab according to the commercial arrangement.
6. NICE TA462: Nivolumab (Opdivo) is recommended as an option for treating relapsed or refractory classical Hodgkin lymphoma in adults after autologous stem cell transplant and treatment with brentuximab vedotin, when the company provides nivolumab according to the commercial arrangement (July 2017).
7. NICE TA655: Nivolumab (Opdivo) is recommended as an option for treating locally advanced or metastatic squamous non-small-cell lung cancer (NSCLC) in adults after chemotherapy (October 2020), only if:
   1. it is stopped at 2 years of uninterrupted treatment, or earlier if their disease progresses and
   2. they have not had a PD‑1 or PD‑L1 inhibitor before
   3. It is recommended only if the company provides nivolumab according to the commercial arrangement.
8. NICE TA713: Nivolumab (Opdivo) is recommended as an option for treating locally advanced or metastatic non-squamous non-small-cell lung cancer (NSCLC) in adults after chemotherapy (July 2021), only if:
   1. their tumours are PD-L1 positive, and
   2. it is stopped at 2 years of uninterrupted treatment, or earlier if their disease progresses, and
   3. they have not had a PD-1 or PD-L1 inhibitor before
   4. It is recommended only if the company provides nivolumab according to the commercial arrangement.
9. NICE TA724: Nivolumab (Opdivo) plus ipilimumab and 2 cycles of platinum-doublet chemotherapy is not recommended, within its marketing authorisation, for untreated metastatic non-small-cell lung cancer (NSCLC) in adults whose tumours have no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations (September 2021).
10. NICE TA876: Nivolumab (​Opdivo​) ​with chemotherapy​ is recommended​, within its marketing authorisation, as an option for the neoadjuvant treatment of resectable (tumours at least 4cm or node positive) non-small-cell lung cancer (NSCLC) in adults, only if the company provides it according to the commercial arrangement (March 2023).
11. NICE TA530: Nivolumab (Opdivo) is not recommended for treating locally advanced unresectable or metastatic urothelial carcinoma in adults who have had platinum-containing therapy (July 2018).
12. NICE TA817: Nivolumab is recommended as an option for the adjuvant treatment of muscle-invasive urothelial cancer that is at high risk of recurrence after radical resection in adults whose tumours express PD-L1 at a level of 1% or more (August 2022), only if:
    1. adjuvant treatment with platinum-based chemotherapy is unsuitable, and
    2. the company provides nivolumab according to the commercial arrangement.
13. NICE TA707: Nivolumab (Opdivo) is recommended, within its marketing authorisation, for treating unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma in adults after fluoropyrimidine and platinum-based therapy (June 2021).
    1. It is recommended only if the company provides nivolumab according to the commercial arrangement.
14. NICE TA746: Nivolumab (Opdivo) is recommended, within its marketing authorisation, for adjuvant treatment of completely resected oesophageal or gastro oesophageal junction cancer in adults who have residual disease after previous neoadjuvant chemoradiotherapy (November 2021).
    1. It is recommended only if the company provides nivolumab according to the commercial arrangement.
15. NICE TA857: Nivolumab (Opdivo) with platinum- and fluoropyrimidine-based chemotherapy is recommended, within its marketing authorisation, as an option for untreated HER2-negative, advanced or metastatic gastric, gastro-oesophageal junction or oesophageal adenocarcinoma in adults whose tumours express PD-L1 with a combined positive score (CPS) of 5 or more, only if it is the company provides it according to the commercial arrangement (January 2023).
16. NICE TA865: Nivolumab (​Opdivo​) with fluoropyrimidine-based and platinum-based combination chemotherapy ​is recommended​ as an option for untreated unresectable advanced, recurrent, or metastatic oesophageal squamous cell carcinoma in adults whose tumours express PD-L1 at a leavel of 1% or more (February 2023), only if:
    1. pembrolizumab plus chemotherapy is not suitable, ​and​
    2. the company provides it according to the commercial arrangement.
17. NICE TA716: Nivolumab (Opdivo) plus ipilimumab (Yervoy) is recommended, within its marketing authorisation, as an option for treating metastatic colorectal cancer with high microsatellite instability (MSI) or mismatch repair (MMR) deficiency after fluoropyrimidine-based combination chemotherapy (July 2021).
    1. It is recommended only if the company provides nivolumab and ipilimumab according to the commercial arrangement
18. NICE TA736: Nivolumab (Opdivo) is recommended as an option for treating recurrent or metastatic squamous cell carcinoma of the head and neck in adults whose disease has progressed on platinum‑based chemotherapy, only if:
    1. the disease has progressed within 6 months of having chemotherapy and
    2. the company provides it according to the commercial arrangement.
19. NICE TA818: Nivolumab (Opdivo) with ipilimumab (Yervoy) is recommended as an option for untreated unresectable malignant pleural mesothelioma in adults (August 2022), only if:
    1. they have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
    2. the company provides it according to the commercial agreement.
20. NICE TA964: Cabozantinib (Cabometyx) with nivolumab (Opdivo) is recommended as an option for untreated advanced renal cell carcinoma in adults (April 2024), only if:
    1. their disease is intermediate or poor risk as defined in the International Metastatic Renal Cell Carcinoma Database Consortium criteria, and
    2. nivolumab with ipilimumab or lenvatinib with pembrolizumab would otherwise be offered, and
    3. the companies provide cabozantinib and nivolumab according to the commercial arrangements.
21. MHRA Drug Safety Update (July 2017): Nivolumab (Opdivo), pembrolizumab (Keytruda): reports of organ transplant rejection
22. MHRA Drug Safety Update (October 2019): Nivolumab (Opdivo), reports of cytomegalovirus (CMV) gastrointestinal infection or reactivation.
    1. Colitis is known to occur commonly in patients treated with nivolumab; advise patients to contact their healthcare professional immediately at the onset of symptoms of colitis (including diarrhoea, blood in stools, or abdominal pain).
    2. If patients on nivolumab present with diarrhoea or colitis, investigate possible causes, including infections; perform a stool infection work-up and screen for cytomegalovirus (CMV).
23. MHRA Drug Safety Update (June 2021): Atezolizumab (Tecentriq) and other immune-stimulatory anti-cancer drugs: risk of severe cutaneous adverse reactions (SCARs) - for more information see update summary at the top of the page.

Nivolumab-relatlimab

• Solution for infusion vials 240mg/20ml / 80mg/20ml

Notes

1. NICE TA950: Nivolumab-relatlimab (Opdualag) is recommended as an option for untreated advanced (unresectable or metastatic) melanoma in people 12 years and over (February 2024), only if:
   1. nivolumab-relatlimab is stopped after 2 years of treatment, or earlier if the cancer progresses, and
   2. the company provides it according to the commercial arrangement.

Pembrolizumab

• Powder for solution for infusion vials 50mg
• Solution for infusion vials 100mg/4ml

Notes

1. NICE TA357: Pembrolizumab (Keytruda) is recommended as an option for treating advanced (unresectable or metastatic) melanoma in adults only (September 2017):
   1. after the disease has progressed with ipilimumab and, for BRAF V600 mutation‑positive disease, a BRAF or MEK inhibitor
   2. when the company provides pembrolizumab in line with the commercial access agreement with NHS England.
2. NICE TA366: Pembrolizumab (Keytruda) is recommended as an option for advanced (unresectable or metastatic) melanoma that has not been previously treated with ipilimumab in adults, only when the company provides pembrolizumab in line with the commercial access agreement with NHS England (September 2017).
3. NICE TA766: Pembrolizumab (Keytruda) is recommended, within its marketing authorisation, as an option for the adjuvant treatment of completely resected stage 3 melanoma with lymph node involvement in adults. It is recommended only if the company provides pembrolizumab according to the commercial arrangement (February 2022).
4. NICE TA837: Pembrolizumab (Keytruda) is recommended, within its marketing authorisation, as an option for the adjuvant treatment of completely resected stage 2B or 2C melanoma in people 12 years and over, only if the company provides it according to the commercial arrangement (October 2022).
5. NICE TA428: Pembrolizumab (Keytruda) is recommended as an option for treating locally advanced or metastatic PD L1 positive non small cell lung cancer in adults who have had at least one chemotherapy (and targeted treatment if they have an epidermal growth factor receptor [EGFR]- or anaplastic lymphoma kinase [ALK]‑positive tumour), only if (September 2017):
   1. pembrolizumab is stopped at 2 years of uninterrupted treatment and no documented disease progression, and
   2. the company provides pembrolizumab in line with the commercial access agreement with NHS England.
6. NICE TA531: Pembrolizumab (Keytruda) is recommended as an option for untreated PD-L1-positive metastatic non-small-cell lung cancer (NSCLC) in adults whose tumours express PD‑L1 (with at least a 50% tumour proportion score) and have no epidermal growth factor receptor- or anaplastic lymphoma kinase-positive mutations, only if (July 2018):
   1. pembrolizumab is stopped at 2 years of uninterrupted treatment and no documented disease progression and
   2. the company provides pembrolizumab according to the commercial access agreement.
7. NICE TA683: Pembrolizumab (Keytruda) with pemetrexed and platinum chemotherapy is recommended as an option for untreated, metastatic, non-squamous non-small-cell lung cancer (NSCLC) in adults whose tumours have no epidermal growth factor receptor (EGFR)‑positive or anaplastic lymphoma kinase (ALK)‑positive mutations (March 2021). This is only if:
   1. it is stopped at 2 years of uninterrupted treatment, or earlier if the disease progresses and
   2. the company provides pembrolizumab according to the commercial arrangement.
8. NICE TA770: Pembrolizumab (Keytruda) with carboplatin and paclitaxel is recommended as an option for untreated metastatic squamous non-small-cell lung cancer (NSCLC) in adults (February 2022), only if
   1. their tumours express PD‑L1 with a tumour proportion score of 0% to 49%
   2. their tumours express PD‑L1 with a tumour proportion score of 50% or more and they need urgent clinical intervention
   3. it is stopped at 2 years of uninterrupted treatment or earlier if their disease progresses and
   4. the company provides pembrolizumab according to the commercial arrangement.
9. NICE TA692: Pembrolizumab (Keytruda) is not recommended, within its marketing authorisation, for treating locally advanced or metastatic urothelial carcinoma in adults who have had platinum-containing chemotherapy (April 2021).
10. NICE TA540: Pembrolizumab (Keytruda) is not recommended for treating relapsed or refractory classical Hodgkin lymphoma in adults who have had autologous stem cell transplant and brentuximab vedotin (September 2018).
11. NICE TA772: Pembrolizumab (Keytruda) is recommended as an option for treating relapsed or refractory classical Hodgkin lymphoma in people aged 3 and older. It is recommended if they have had an autologous stem cell transplant that has not worked or they have had at least 2 previous therapies and an autologous stem cell transplant is not an option (February 2022), and only if:
    1. they have not had brentuximab vedotin and
    2. the company provides pembrolizumab according to the commercial arrangement.
12. NICE TA967: Pembrolizumab (Keytruda) is recommended as an option for treating relapsed or refractory classical Hodgkin lymphoma in people 3 years and over who have had at least 2 previous treatments and cannot have an autologous stem cell transplant (ASCT) (May 2024), only if:
    1. they have already had brentuximab vedotin and
    2. pembrolizumab is stopped after 2 years of treatment or earlier if the person has a stem cell transplant or the disease progresses and
    3. the company provides it according to the commercial arrangement.
13. NICE TA650: Pembrolizumab (Keytruda) with axitinib (Inlyta) is not recommended, within its marketing authorisation, for untreated advanced renal cell carcinoma in adults (September 2020).
14. NICE TA830: Pembrolizumab (Keytruda) is recommended, within its marketing authorisation, as an option for the adjuvant treatment of renal cell carcinoma at increased risk of recurrence after nephrectomy, with or without metastatic lesion resection, in adults, only if the company provides it according to the commercial arrangement (October 2022).
15. NICE TA661: Pembrolizumab (Keytruda) is recommended as an option for untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) in adults whose tumours express PD‑L1 with a combined positive score (CPS) of 1 or more, only when the criteria of the NICE TA are met (November 2020).
16. NICE TA709: Pembrolizumab (Keytruda) is recommended as an option for untreated metastatic colorectal cancer with high microsatellite instability (MSI) or mismatch repair (MMR) deficiency in adults (June 2021), only if:
    1. pembrolizumab is stopped after 2 years and no documented disease progression, and
    2. the company provides pembrolizumab according to the commercial arrangement.
17. NICE TA737: Pembrolizumab (Keytruda) with platinum- and fluoropyrimidine-based chemotherapy is recommended, within its marketing authorisation, as an option for untreated locally advanced unresectable or metastatic carcinoma of the oesophagus in adults whose tumours express PD‑L1 with a combined positive score (CPS) of 10 or more, only if the company provides it according to the commercial arrangement (October 2021).
18. NICE TA801: Pembrolizumab (Keytruda) plus chemotherapy (paclitaxel or nab-paclitaxel) is recommended as an option for treating triple-negative, locally recurrent unresectable or metastatic breast cancer in adults who have not had chemotherapy for metastatic disease (June 2022), and only if:
    1. the tumours express PD-L1 with a combined positive score (CPS) of 10 or more and an immune cell staining (IC) of less than 1%, and
    2. the company provides pembrolizumab according to the commercial arrangement.
19. NICE TA851: Pembrolizumab (Keytruda) is recommended, within its marketing authorisation, as an option with chemotherapy for neoadjuvant treatment and then continued alone as adjuvant treatment after surgery for adults with triple-negative early breast cancer at high risk of recurrence OR locally advanced breast cancer (December 2022).
20. NICE TA858: Lenvatinib (Kisplyx) with pembrolizumab (Keytruda) is recommended as an option for untreated advanced renal cell carcinoma in adults (January 2023), only if:
    1. their disease is intermediate or poor risk as defined in the International Metastatic Renal Cell Carcinoma Database Consortium criteria and
    2. nivolumab with ipilimumab would otherwise be offered and
    3. the companies provide lenvatinib and pembrolizumab according to the commercial arrangements.
21. NICE TA904: Pembrolizumab (Keytruda) plus lenvatinib is recommended, within its marketing authorisation, for treating advanced or recurrent endometrial cancer in adults (June 2023):
    1. whose cancer has progressed on or after platinum-based chemotherapy and
    2. who cannot have curative surgery or radiotherapy and
    3. the company provides it according to the commercial arrangements.
22. NICE TA914: Pembrolizumab (Keytruda) is recommended as an option for treating tumours with high microsatellite instability (MSI) or mismatch repair (MMR) deficiency in adults with; a) advanced or recurrent endometrial cancer that has progressed during or after a platinum-based therapy, who cannot have curative surgery or radiotherapy; b) unresectable or metastatic gastric, small intestine or biliary cancer that has progressed during or after 1 therapy; or c) colorectal cancer after fluoropyrimidine combination therapy, only if they cannot have nivolumab with ipilimumab (September 2023); only if:
    1. pembrolizumab is stopped at 2 years of uninterrupted treatment, or earlier if the cancer progressed, and
       
    2. the company provides it according to the commercial arrangement.
23. NICE TA939: Pembrolizumab (Keytruda) plus chemotherapy with or without bevacizumab is recommended as an option for treating persistent, recurrent or metastatic cervical cancer in adults whose tumours express PD-L1 with a combined positive score of at least 1 (December 2023), only if:
    1. pembrolizumab is stopped at 2 years of uninterrupted treatment, or earlier if the cancer progresses, and
    2. the company provides is according to the commercial arrangements.
24. NICE TA983: Pembrolizumab (Keytruda) with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy is not recommended, within its marketing authorisation, for untreated locally advanced unresectable or metastatic HER2-positive gastric or gastro-oesophageal junction (GOJ) adenocarcinoma in adults whose tumours express PD-L1 with a combined positive score (CPS) of 1 or more (June 2024).
25. NICE TA997: Pembrolizumab (Keytruda) with platinum- and fluoropyrimidine-based chemotherapy is recommended, within its marketing authorisation, as an option for untreated locally advanced unresectable or metastatic HER2-negative gastric or gastro-oesophageal junction adenocarcinoma in adults whose tumours express PD-L1 with a combined positive score (CPS) of 1 or more, only if the company provides it according to the commercial arrangement (August 2024).
26. MHRA Drug Safety Update (July 2017): Nivolumab (Opdivo), pembrolizumab (Keytruda): reports of organ transplant rejection.
27. MHRA Drug Safety Update (June 2021): Atezolizumab (Tecentriq) and other immune-stimulatory anti-cancer drugs: risk of severe cutaneous adverse reactions (SCARs) - for more information see update summary at the top of the page.

CD19 monoclonal antibodies

Loncastuximab tesirine

• Powder for solution for infusion vials 10mg

Notes

1. NICE TA947: Loncastuximab tesirine (Zynlonta) is recommended as an option for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) after 2 or more systemic treatments in adults (January 2024), only if:
   1. they have previously had polatuzumab vedotin, or if polatuzumab vedotin is contraindicated or not tolerated, and
   2. the company provides it according to the commercial arrangement.

Tafasitamab

• NICE TA883: Tafasitamib (​Minjuvi​) with lenalidomide is ​not recommended​, within its marketing authorisation, for treating relapsed or refractory diffuse large B-cell lymphoma in adults who cannot have an autologous stem cell transplant (May 2023).

CD20 monoclonal antibodies

Obinutuzumab

• Solution for infusion vials 1g/40ml

Notes

1. NICE TA343: Obinutuzumab (Gazyvaro), in combination with chlorambucil is recommended as an option for adults with untreated chronic lymphocytic leukaemia who have comorbidities that make full‑dose fludarabine‑based therapy unsuitable for them (June 2015), only if:
   1. bendamustine-based therapy is not suitable and
   2. the company provides obinutuzumab with the discount agreed in the patient access scheme.
2. NICE TA513: Obinutuzumab (Gazyvaro) is recommended as an option for untreated advanced follicular lymphoma in adults (that is, first as induction treatment with chemotherapy, then alone as maintenance therapy), only when the criteria of the NICE TA are met (March 2018).
3. NICE TA629: Obinutuzumab (Gazyvaro) with bendamustine followed by obinutuzumab maintenance is recommended, within its marketing authorisation, as an option for treating follicular lymphoma that did not respond or progressed up to 6 months after treatment with rituximab or a rituximab-containing regimen. It is recommended only if the company provides it according to the commercial arrangement (May 2020).
4. MHRA Drug Safety Update (August 2014): Ofatumumab: reminder of risk of serious and fatal infusion reactions with ofatumumab and other anti-CD20 monoclonal antibodies. Always give premedication before each ofatumumab infusion. If a severe reaction occurs, interrupt ofatumumab infusion and treat the reaction.
   1. Infusion reactions have also occurred with other anti-CD20 monoclonal antibodies such as rituximab (MabThera) and obinutuzumab (Gazyvaro).
5. MHRA Drug Safety Update (March 2021): Bendamustine (Levact): increased risk of non-melanoma skin cancer and progressive multifocal encephalopathy (PML).
   1. Very rare cases of PML have also been reported in patients being treated with bendamustine usually in combination with rituximab or obinutuzumab
   2. Periodically perform skin examinations in patients on bendamustine-containing regimen.s

Ocrelizumab

• Concentrate for solution for infusion 300mg/10ml

Notes

1. NICE TA533: Ocrelizumab (Ocrevus) is recommended as an option for treating relapsing-remitting multiple sclerosis in adults with active disease defined by clinical or imaging features, only when the criteria of the NICE TA are met (July 2018)
2. NICE TA585: Ocrelizumab (Ocrevus) is recommended, within its marketing authorisation, as an option for treating early primary progressive multiple sclerosis with imaging features characteristic of inflammatory activity in adults (June 2019)

Ofatumumab

• Solution for injection in pre-filled pens 20mg

Notes

1. NICE TA699: Ofatumumab (Kesimpta) is recommended as an option for treating relapsing–remitting multiple sclerosis in adults with active disease defined by clinical or imaging features (May 2021)
   1. This is only if the company provides ofatumumab according to the commercial arrangement
2. MHRA Drug Safety Update (January 2014): Ofatumumab: screen for hepatitis B virus before treatment.
   1. Patients with active infection with this virus should not be treated with ofatumumab
   2. Patients with positive hepatitis B serology (but no active disease) should be referred to a specialist in liver disease for consultation about monitoring and initiation of antiviral treatment for hepatitis B before starting treatment with ofatumumab
3. MHRA Drug Safety Update (August 2014): Ofatumumab: reminder of risk of serious and fatal infusion reactions with ofatumumab and other anti-CD20 monoclonal antibodies. Always give premedication before each ofatumumab infusion. If a severe reaction occurs, interrupt ofatumumab infusion and treat the reaction

Rituximab

• Solution for infusion vials 10mg/1ml
• Solution for subcutaneous injection vials 1.4mg/11.7ml

Notes

1. The commissioning of rituximab in combination with methotrexate is accepted in Devon as a first line biological treatment option for patients with rheumatoid arthritis who have had an inadequate response to conventional DMARDs, including methotrexate, and for whom TNF inhibitors are not clinically appropriate due to comorbidities which give rise to medical concerns (see Commissioning Policy for more details).
2. The commissioning of rituximab without methotrexate is accepted in Devon as a first line biological treatment option for patients who have had an inadequate response to conventional DMARDs, who cannot receive methotrexate, and for whom TNF inhibitors are not clinically appropriate due to comorbidities which give rise to medical concerns (see Commissioning Policy for more details).
3. NICE TA308: Rituximab (MabThera), in combination with glucocorticoids, is recommended as an option for inducing remission in adults with anti-neutrophil cytoplasmic antibody [ANCA]-associated vasculitis (severely active granulomatosis with polyangiitis [Wegener's] and microscopic polyangiitis), only when the criteria of the NICE ta are met (March 2014).
4. NICE TA195: Adalimumab, etanercept, infliximab, rituximab, and abatacept for the treatment of rheumatoid arthritis after the failure of a TNF inhibitor (August 2010):
   1. Rituximab (MabThera) in combination with methotrexate is recommended as an option for the treatment of adults with severe active rheumatoid arthritis who have had an inadequate response to, or are intolerant of, other disease-modifying anti-rheumatic drugs (DMARDs), including at least one tumour necrosis factor (TNF) inhibitor.
   2. Refer to TA195 for continuation criteria and other considerations.
5. NICE TA243: Rituximab for the first-line treatment of stage III-IV follicular lymphoma (January 2012):
   1. Rituximab, is recommended as an option for the treatment of symptomatic stage III and IV follicular lymphoma in previously untreated people in combination with:
      1. cyclophosphamide, vincristine and prednisolone (CVP)
      2. cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP)
      3. mitoxantrone, chlorambucil and prednisolone (MCP)
      4. cyclophosphamide, doxorubicin, etoposide, prednisolone and interferon-α (CHVPi) or
      5. chlorambucil.
6. NICE TA137: Rituximab for the treatment of relapsed or refractory stage III or IV follicular non-Hodgkin's lymphoma (February 2008):
   1. Rituximab, within its marketing authorisation, in combination with chemotherapy, is recommended as an option for the induction of remission in people with relapsed stage III or IV follicular non-Hodgkin's lymphoma.
   2. Rituximab monotherapy as maintenance therapy, within its marketing authorisation, is recommended as an option for the treatment of people with relapsed stage III or IV follicular non-Hodgkin's lymphoma in remission induced with chemotherapy with or without rituximab.
   3. Rituximab monotherapy, within its marketing authorisation, is recommended as an option for the treatment of people with relapsed or refractory stage III or IV follicular non-Hodgkin's lymphoma, when all alternative treatment options have been exhausted (that is, if there is resistance to or intolerance of chemotherapy).
7. NICE TA193: Rituximab in combination with fludarabine and cyclophosphamide is recommended as a treatment option for people with relapsed or refractory chronic lymphocytic leukaemia, only when the criteria of the NICE TA are met (July 2010).
8. NICE TA226: Rituximab (MabThera) maintenance therapy is recommended as an option for the treatment of people with follicular non-Hodgkin’s lymphoma that has responded to first-line induction therapy with rituximab in combination with chemotherapy (June 2011).
9. NICE TA174: Rituximab for the first-line treatment of chronic lymphocytic leukaemia (July 2009):
   1. Rituximab in combination with fludarabine and cyclophosphamide is recommended as an option for the first-line treatment of chronic lymphocytic leukaemia in people for whom fludarabine in combination with cyclophosphamide is considered appropriate.
   2. Rituximab in combination with chemotherapy agents other than fludarabine and cyclophosphamide is not recommended for the first-line treatment of chronic lymphocytic leukaemia.
10. NICE TA359: Idelalisib (Zydelig) in combination with rituximab, is recommended (October 2015):
    1. for untreated chronic lymphocytic leukaemia in adults with a 17p deletion or TP53 mutation or
    2. for chronic lymphocytic leukaemia in adults when the disease has been treated but has relapsed within 24 months.
11. NICE TA561: Venetoclax (Venclyxto) with rituximab is recommended, as an option for treating chronic lymphocytic leukaemia in adults who have had at least 1 previous therapy (February 2019).
12. Rituximab NHS England Specialised Commissioning Documents:
    1. Non routinely commissioned policies
    2. Routinely commissioned policies
    3. Policy statements / urgent policy statements
13. MHRA Drug Safety Update (December 2009): Rituximab: progressive multifocal leukoencephalopathy in a patient. A case of progressive multifocal leukoencephalopathy (PML) with a fatal outcome was reported in a patient with rheumatoid arthritis who had not previously received treatment with methotrexate or a TNF antagonist.
14. MHRA Drug Safety Update (December 2013): Rituximab: screen for hepatitis B virus before treatment. Screening for hepatitis B virus is now recommended in all patients (not only those at risk of this infection) before starting treatment for all indications.
15. MHRA Drug Safety Update (August 2014): Ofatumumab: reminder of risk of serious and fatal infusion reactions with ofatumumab and other anti-CD20 monoclonal antibodies. Always give premedication before each ofatumumab infusion. If a severe reaction occurs, interrupt ofatumumab infusion and treat the reaction.
    1. Infusion reactions have also occurred with other anti-CD20 monoclonal antibodies such as rituximab (MabThera) and obinutuzumab (Gazyvaro). Specific recommendations to reduce the risk of infusion reactions for each of these products, including the use of pre-medications, are in the summary of product characteristics for each product.
16. MHRA Drug Safety Update (March 2021): Bendamustine (Levact): increased risk of non-melanoma skin cancer and progressive multifocal encephalopathy (PML).
    1. Very rare cases of PML have also been reported in patients being treated with bendamustine usually in combination with rituximab or obinutuzumab.
    2. Periodically perform skin examinations in patients on bendamustine-containing regimens.

Ublituximab

• Concentrate for solution for infusion 150mg/6ml

Notes

1. NICE TA1025: Ublituximab (Briumvi) is recommended as an option for treating relapsing forms of multiple sclerosis, defined as active by clinical or imaging features in adults, only if the multiple sclerosis is relapsing-remitting, and the company provides it according to the commercial arrangement (December 2024).

Mosunetuzumab

• NICE TA892: Mosunetuzumab (Lunsumio) is ​not recommended​, within its marketing authorisation, for treating relapsed or refractory follicular lymphoma in adults who have had 2 or more systemic therapies.

CD20/CD3 monoclonal antibodies

Epcoritamab

• Solution for injection vials 4mg/0.8ml, 48mg/0.8ml

Notes

1. NICE TA954: Epcoritamab (Tepkinly) is recommended as an option for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in adults after 2 or more systemic treatments (March 2024), only if:
   1. they have had polatuzumab vedotin, or if polatuzumab vedotin is contraindicated or not tolerated, and
   2. the company provides it according to the commercial arrangement.

Glofitamab

• Solution for infusion vials 2.5mg/2.5ml, 10mg/10ml

Notes

1. NICE TA927: Glofitamab (Columvi) is recommended, within its marketing authorisation, as an option for treating relapsed or refractory diffuse large B-cell lymphoma in adults after 2 or more systemic treatments, only if the company provides it according to the commercial arrangement (October 2023).
   

CD22 monoclonal antibodies

Inotuzumab ozogamicin

• Powder for solution for infusion vials 1mg

Notes

1. NICE TA541: Inotuzumab ozogamicin (Besponsa) is recommended, within its marketing authorisation, as an option for treating relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukaemia in adults. People with relapsed or refractory Philadelphia-chromosome-positive disease should have had at least 1 tyrosine kinase inhibitor (September 2018).
   1. Inotuzumab ozogamicin is recommended only if the company provides it according to the commercial arrangement.

CD30 monoclonal antibodies

Brentuximab vedotin

• Powder for solution for infusion vials 50mg

Notes

1. NICE TA478: Brentuximab vedotin (Adcetris) is recommended as an option for treating relapsed or refractory systemic anaplastic large cell lymphoma in adults, only when the criteria of the NICE TA are met (October 2017).
2. NICE TA641: Brentuximab vedotin (Adcetris) with cyclophosphamide, doxorubicin and prednisone (CHP) is recommended, within its marketing authorisation, as an option for untreated systemic anaplastic large cell lymphoma in adults. It is only recommended if the company provides brentuximab vedotin according to the commercial arrangement. (August 2020).
3. NICE TA524: Brentuximab vedotin (Adcetris) is recommended as an option for treating CD30 positive Hodgkin lymphoma in adults with relapsed or refractory disease, only when the criteria of the NICE TA are met (June 2018).
4. NICE TA577: Brentuximab vedotin (Adcetris) is recommended as an option for treating CD30‑positive cutaneous T‑cell lymphoma (CTCL) after at least 1 systemic therapy in adults, only when the criteria of the NICE TA are met (April 2019).

CD33 monoclonal antibodies

Gemtuzumab ozogamicin

• Powder for solution for infusion vials 5mg

Notes

1. NICE TA545: Gemtuzumab ozogamicin (Mylotarg), with daunorubicin and cytarabine, is recommended as an option for untreated de novo CD33-positive acute myeloid leukaemia (AML), except acute promyelocytic leukaemia, in people 15 years and over, only when the criteria of the NICE TA are met (November 2018).

CD38 monoclonal antibodies

Daratumumab

• Solution for injection vials 100mg/5ml, 400mg/20ml, 1.8g/15ml

Notes

1. NICE TA763: Daratumumab (Darzalex) plus bortezomib, thalidomide and dexamethasone is recommended, within its marketing authorisation, as induction and consolidation treatment for untreated multiple myeloma in adults, when an autologous stem cell transplant is suitable. It is recommended only if the company provides daratumumab according to the commercial arrangement (February 2022).
   
2. NICE TA783: Daratumumab (Darzalex) monotherapy is recommended as an option for treating relapsed and refractory multiple myeloma in adults who have had a proteasome inhibitor and an immunomodulator, and whose disease progressed on the last treatment (April 2022), only if:
   
   1. they have daratumumab after 3 treatments and
   2. the company provides daratumumab according to the commercial arrangement.
3. ​NICE TA897: Daratumumab (​Darzalex​) with bortezomib and dexamethasone ​is recommended​ as an option for treating multiple myeloma in adults (June 2023), only if they have had just 1 previous line of treatment ​and​:
   1. it included lenalidomide ​or​
   2. lenalidomide is unsuitable as a second-line treatment, ​and​
   3. the company provides it according to the commercial arrangement.
4. NICE TA917: Daratumumab (Darzalex) with lenalidomide and dexamethadone is recommended, within its marketing authorisation, as an option for untreated multiple myeloma in adults, when an autologous stem cell transplant is unsuitable, only if the company provides it according to the commercial arrangement (October 2023).
5. NICE TA959: Daratumumab (Darzalex) plus bortezomib, cyclophosphamide and dexamethasone is recommended as an option for treating newly diagnosed systemic amyloid light-chain (AL) amyloidosis in adults (March 2024), only if:
   1. daratumumab is stopped after 24 cycles of treatment, or earlier if the condition progresses, and
   2. the company provides it according to the commercial arrangement.
6. MHRA Drug Safety Update (August 2019): Daratumumab (Darzalex): risk of reactivation of hepatitis B virus. Establish hepatitis B virus status before initiating daratumumab and in patients with unknown hepatitis B virus serology who are already being treated with daratumumab.

Isatuximab

• Solution for infusion vials 100mg/5ml, 500mg/25ml

Notes

1. NICE TA658: Isatuximab (Sarclisa), plus pomalidomide and dexamethasone, is recommended for use within the Cancer Drugs Fund as an option for treating relapsed and refractory multiple myeloma in adults who have had lenalidomide and a proteasome inhibitor, and whose disease has progressed on their last treatment (November 2020), only if:
   1. they have had 3 previous lines of treatment
   2. the conditions in the managed access agreement for isatuximab plus pomalidomide and dexamethasone are followed.

CD52 monoclonal antibodies

Alemtuzumab

• Solution for infusion vials 12mg/1.2ml

Notes

1. NICE TA312: Alemtuzumab (Lemtrada) is recommended as an option, within its marketing authorisation, for treating highly active relapsing–remitting multiple sclerosis in adults (May 2014) with:
   1. highly active disease despite a full and adequate course of treatment with at least 1 disease-modifying therapy or
   2. rapidly-evolving severe relapsing-remitting multiple sclerosis defined by 2 or more relapses in the previous year, and baseline MRI evidence of disease activity.
2. MHRA Drug Safety Update (February 2020): Alemtuzumab (Lemtrada): updated restrictions and strengthened monitoring requirements following review of serious cardiovascular and immune-mediated reactions:
   1. Alemtuzumab should only be used as a single disease-modifying therapy in adults under the conditions specified in the Safety Update
   2. New contraindications – for further information see Safety Update
   3. Revised monitoring requirements before, during and after treatment – for further information see Safety Update.
   4. Monitor patients for autoimmune conditions for at least 48 months after the last infusion – some autoimmune reactions have been reported after this routine monitoring period
   5. Patients receiving alemtuzumab should seek urgent medical attention if they develop any of the signs or symptoms of a serious adverse reaction.

IgG4 monoclonal antibodies

Lebrikizumab

• Solution for injection pre-filled pens 250mg/2ml
• Solution for injection pre-filled syringes 250mg/2ml

Notes

1. NICE TA986: Lebrikizumab (Ebglyss) is recommended as an option for treating moderate to severe atopic dermatitis that is suitable for systemic treatment in people 12 years and over with a body weight of 40kg or more (July 2024), only if:
   1. the atopic dermatitis has not responded to at least 1 systemic immunosuppressant or these treatments are not suitable, and
   2. dupilumab or tralokinumab would otherwise be offered, and
   3. the company provides it according to the commercial arrangement.
   4. Refer to TA986 for discontinuation criteria.

Antibody-drug conjugate

Sacituzumab govitecan

• Powder for concentrate for solution for infusion vials 180mg

Notes

1. NICE TA819: Sacituzumab govetican (Trodelvy) is recommended, within its marketing authorisation, as an option for treating unresectable triple-negative locally advanced or metastatic breast cancer in adults after 2 or more systemic therapies, at least 1 of which was for advanced disease. It is recommended only if the company provides sacituzumab govitecan according to the commercial arrangement (August 2022).