Table 2, Responses to Questions From the Drug Programs - Mogamulizumab (Poteligeo)

Implementation issues	Response
Relevant comparators
The comparator in the pivotal trial, MAVORIC, is vorinostat which is not publicly funded in Canada. It is noted the pERC conditionally recommended brentuximab vedotin for the treatment of adult patients with CD30+ mycosis fungoides who have had one prior systemic therapy in December 2020. This treatment is funded in some provinces. There is no standard of care for the treatment of MF or SS in patients who progress after one prior systemic therapy. Public funding of treatments varies across provinces.	pERC acknowledged that vorinostat is not publicly funded in Canada and that there is no standard of care for the treatment of MF or SS in patients who progress after one prior systemic therapy. pERC noted that public funding of treatments varies across provinces and discussed the availability of brentuximab vedotin for the treatment of adult patients with CD30+ mycosis fungoides who have had one prior systemic therapy which is available only is some provinces.
How does mogamulizumab compare to brentuximab vedotin for patients with CD30+ MF? Should these drugs be sequenced and if so, is there a preferred order?	pERC noted that brentuximab vedotin is available in some jurisdictions and that patients are required to have CD30+ immunohistochemical expression for treatment with brentuximab vedotin. As a result, pERC agreed with the clinical experts that brentuximab vedotin would be sequenced ahead of mogamulizumab in patients with CD30+ MF in jurisdictions where brentuximab vedotin. pERC also noted that CD30+ is seldomly expressed in SS, and patients with SS are not eligible for brentuximab under Canadian funding models.
Considerations for initiation of therapy
The MAVORIC trial enrolled patients with stage IB-IV previously treated with systemic therapy. Should funding criteria include staging information?	pERC agreed with the clinical experts that aside from patients with stage IA, who were not eligible for the MAVORIC trial, funding criteria should not include staging information, as the primary outcome of the MAVORIC trial demonstrated improved PFS across all included stages (IB-IV) and was not powered to detect differences by stage. However, the clinical experts noted that there was a clearer benefit observed in the MAVORIC trial for advanced stages (III-IV).
MAVORIC enrolled patients with ECOG 0 to 1. Is it reasonable to treat patients with ECOG 2 or greater with mogamulizumab?	pERC noted that patients with ECOG 2 were not eligible for the MAVORIC trial and agreed with the clinical experts that this may not be reflective of Canadian clinical practice for MF/SS particularly for those with advanced stage, and multiply relapsed disease. pERC agreed with the clinical experts that treatment of mogamulizumab in these patients should be left to the discretion of the treating clinician.
MAVORIC excluded patients with CNS metastasis, significant cardiac disease (class III or IV NYHA) and large cell transformation. Should these patients be eligible for mogamulizumab?	pERC acknowledged the clinical expert’s statement that it is currently unclear whether patients with CNS metastases or significant cardiac disease should be excluded from using mogamulizumab. pERC agreed with the clinical experts that due to safety concerns, prescribing for advanced heart failure is a concern and that physicians should use discretion in this population. The clinical experts stated that mogamulizumab would not be prescribed in the absence of future or additional data supporting use in patients with CNS metastases. Ultimately, pERC felt that mogamulizumab should not be initiated in patients with active (untreated or uncontrolled) CNS metastases. pERC acknowledged the clinical expert’s statement that large cell transformation is a clinical challenge in the management of MF, with no standard of care, and a generally poor prognosis. pERC noted that the MAVORIC trial was amended to allow patients who developed large cell transformation while on vorinostat to cross over to mogamulizumab, provided they met all other eligibility criteria. As a result, pERC agreed with the clinical experts that patients with large cell transformation should be considered for mogamulizumab provided they meet other eligibility criteria.
The majority of patients in the MAVORIC trial failed more than 1 prior systemic therapy. Should patients be required to have failed more than one prior systemic therapy to be eligible for mogamulizumab?	pERC agreed with the clinical experts that in line with the MAVORIC trial, patients in Canada are likely to have received multiple prior systemic therapies. There is no concern surrounding the use of mogamulizumab in patients that have failed multiple systemic therapies.
In MAVORIC, patients with a global complete response could continue treatment for up to 12 months or until progression, whichever came first. Upon relapse, would these patients be eligible for retreatment and if so, if there a reasonable time frame (i.e., patients must have been off therapy for a minimum time frame to be eligible for retreatment)?	pERC noted that there is currently no evidence to support retreatment with mogamulizumab in patients who relapse and noted that only 4 patients in the MAVORIC trial achieved a complete response. However, the clinical experts noted that patients with cutaneous lymphoma can be retreated with prior therapies and still achieve a response. As a result, pERC felt that retreatment may be reasonable on a case-by-case review by province.
Considerations for prescribing of therapy
Mogamulizumab 1 mg/kg IV over 60 minutes on days 1, 8, 15 and 22 of the first 28 days cycle and then days 1 and 15 q28 days thereafter. Treatment continued until disease progression, unacceptable toxicity. Mogamulizumab is supplied as 20 mg vials with potential for wastage.	pERC acknowledged the potential for wastage.
Generalizability
Should patients currently receiving a second-line systemic therapy be eligible to switch to mogamulizumab?	pERC agreed with the clinical experts that if current treatment is effective and well tolerated, switching to mogamulizumab is not required. In line with the clinical trial, patients would be eligible to switch following failure of systemic therapy.
Funding algorithm (oncology only)
Drug may change place in therapy of comparator drugs. Brentuximab vedotin for the treatment of adult patients with CD30+ mycosis fungoides who have had 1 prior systemic therapy.	pERC agreed with the clinical experts that brentuximab vedotin would be sequenced ahead of mogamulizumab in patients with CD30+ MF in jurisdictions where brentuximab vedotin is available for patients with CD30+ MF.
Care provision issues
Potential for infusion reactions (grade 1 to 2 incidence 32%, grade 3 incidence 2%). Drug rashes are common and must be monitored for.	pERC acknowledged the potential for infusion reactions and that drug rashes common. pERC noted that as per Health Canada Product Monograph, mogamulizumab should be discontinued for life-threatening (Grade 4) rash or (Grade 4) infusion reactions.
Preparation of mogamulizumab requires a sterile compounding pharmacy and has limited final product stability. As such, administration of mogamulizumab is likely to be restricted to facilities/locations with access to a sterile compounding pharmacy on site.	The storage, stability, and disposal guidance of mogamulizumab is stated in the Health Canada product monograph.
System and economic issues
Brentuximab vedotin for previously treated CD30+ MF has confidential pricing (pCPA).	pERC noted that brentuximab vedotin is available for patients with CD30+ MF in some jurisdictions.

Implementation issues

Response

Relevant comparators

The comparator in the pivotal trial, MAVORIC, is vorinostat which is not publicly funded in Canada.

It is noted the pERC conditionally recommended brentuximab vedotin for the treatment of adult patients with CD30+ mycosis fungoides who have had one prior systemic therapy in December 2020. This treatment is funded in some provinces.

There is no standard of care for the treatment of MF or SS in patients who progress after one prior systemic therapy. Public funding of treatments varies across provinces.

pERC acknowledged that vorinostat is not publicly funded in Canada and that there is no standard of care for the treatment of MF or SS in patients who progress after one prior systemic therapy. pERC noted that public funding of treatments varies across provinces and discussed the availability of brentuximab vedotin for the treatment of adult patients with CD30+ mycosis fungoides who have had one prior systemic therapy which is available only is some provinces.

How does mogamulizumab compare to brentuximab vedotin for patients with CD30+ MF? Should these drugs be sequenced and if so, is there a preferred order?

pERC noted that brentuximab vedotin is available in some jurisdictions and that patients are required to have CD30+ immunohistochemical expression for treatment with brentuximab vedotin. As a result, pERC agreed with the clinical experts that brentuximab vedotin would be sequenced ahead of mogamulizumab in patients with CD30+ MF in jurisdictions where brentuximab vedotin. pERC also noted that CD30+ is seldomly expressed in SS, and patients with SS are not eligible for brentuximab under Canadian funding models.

Considerations for initiation of therapy

The MAVORIC trial enrolled patients with stage IB-IV previously treated with systemic therapy. Should funding criteria include staging information?

pERC agreed with the clinical experts that aside from patients with stage IA, who were not eligible for the MAVORIC trial, funding criteria should not include staging information, as the primary outcome of the MAVORIC trial demonstrated improved PFS across all included stages (IB-IV) and was not powered to detect differences by stage. However, the clinical experts noted that there was a clearer benefit observed in the MAVORIC trial for advanced stages (III-IV).

MAVORIC enrolled patients with ECOG 0 to 1. Is it reasonable to treat patients with ECOG 2 or greater with mogamulizumab?

pERC noted that patients with ECOG 2 were not eligible for the MAVORIC trial and agreed with the clinical experts that this may not be reflective of Canadian clinical practice for MF/SS particularly for those with advanced stage, and multiply relapsed disease.

pERC agreed with the clinical experts that treatment of mogamulizumab in these patients should be left to the discretion of the treating clinician.

MAVORIC excluded patients with CNS metastasis, significant cardiac disease (class III or IV NYHA) and large cell transformation. Should these patients be eligible for mogamulizumab?

pERC acknowledged the clinical expert’s statement that it is currently unclear whether patients with CNS metastases or significant cardiac disease should be excluded from using mogamulizumab. pERC agreed with the clinical experts that due to safety concerns, prescribing for advanced heart failure is a concern and that physicians should use discretion in this population.

The clinical experts stated that mogamulizumab would not be prescribed in the absence of future or additional data supporting use in patients with CNS metastases. Ultimately, pERC felt that mogamulizumab should not be initiated in patients with active (untreated or uncontrolled) CNS metastases.

pERC acknowledged the clinical expert’s statement that large cell transformation is a clinical challenge in the management of MF, with no standard of care, and a generally poor prognosis. pERC noted that the MAVORIC trial was amended to allow patients who developed large cell transformation while on vorinostat to cross over to mogamulizumab, provided they met all other eligibility criteria. As a result, pERC agreed with the clinical experts that patients with large cell transformation should be considered for mogamulizumab provided they meet other eligibility criteria.

The majority of patients in the MAVORIC trial failed more than 1 prior systemic therapy. Should patients be required to have failed more than one prior systemic therapy to be eligible for mogamulizumab?

pERC agreed with the clinical experts that in line with the MAVORIC trial, patients in Canada are likely to have received multiple prior systemic therapies. There is no concern surrounding the use of mogamulizumab in patients that have failed multiple systemic therapies.

In MAVORIC, patients with a global complete response could continue treatment for up to 12 months or until progression, whichever came first. Upon relapse, would these patients be eligible for retreatment and if so, if there a reasonable time frame (i.e., patients must have been off therapy for a minimum time frame to be eligible for retreatment)?

pERC noted that there is currently no evidence to support retreatment with mogamulizumab in patients who relapse and noted that only 4 patients in the MAVORIC trial achieved a complete response. However, the clinical experts noted that patients with cutaneous lymphoma can be retreated with prior therapies and still achieve a response. As a result, pERC felt that retreatment may be reasonable on a case-by-case review by province.

Considerations for prescribing of therapy

Mogamulizumab 1 mg/kg IV over 60 minutes on days 1, 8, 15 and 22 of the first 28 days cycle and then days 1 and 15 q28 days thereafter. Treatment continued until disease progression, unacceptable toxicity.

Mogamulizumab is supplied as 20 mg vials with potential for wastage.

pERC acknowledged the potential for wastage.

Generalizability

Should patients currently receiving a second-line systemic therapy be eligible to switch to mogamulizumab?

pERC agreed with the clinical experts that if current treatment is effective and well tolerated, switching to mogamulizumab is not required. In line with the clinical trial, patients would be eligible to switch following failure of systemic therapy.

Funding algorithm (oncology only)

Drug may change place in therapy of comparator drugs. Brentuximab vedotin for the treatment of adult patients with CD30+ mycosis fungoides who have had 1 prior systemic therapy.

pERC agreed with the clinical experts that brentuximab vedotin would be sequenced ahead of mogamulizumab in patients with CD30+ MF in jurisdictions where brentuximab vedotin is available for patients with CD30+ MF.

Care provision issues

Potential for infusion reactions (grade 1 to 2 incidence 32%, grade 3 incidence 2%). Drug rashes are common and must be monitored for.

pERC acknowledged the potential for infusion reactions and that drug rashes common. pERC noted that as per Health Canada Product Monograph, mogamulizumab should be discontinued for life-threatening (Grade 4) rash or (Grade 4) infusion reactions.

Preparation of mogamulizumab requires a sterile compounding pharmacy and has limited final product stability. As such, administration of mogamulizumab is likely to be restricted to facilities/locations with access to a sterile compounding pharmacy on site.

The storage, stability, and disposal guidance of mogamulizumab is stated in the Health Canada product monograph.

System and economic issues

Brentuximab vedotin for previously treated CD30+ MF has confidential pricing (pCPA).

pERC noted that brentuximab vedotin is available for patients with CD30+ MF in some jurisdictions.

From: Mogamulizumab (Poteligeo)

Mogamulizumab (Poteligeo): CADTH Reimbursement Recommendation: Indication: Relapsed or refractory mycosis fungoides or Sézary syndrome after at least 1 prior systemic therapy [Internet].

Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2022 Aug.

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Table 2Responses to Questions From the Drug Programs