BLENREP payable by health insurer in heavily pretreated refractory MM.

Belantamab mafodotin (BLENREP) is the first and only BCMA*-targeted antibody-drug conjugate to be approved in Switzerland in June 2022, and has been reimbursable since November 2022 for the treatment of multiple myeloma in heavily pretreated adult patients who experienced disease progression during their last therapy [1,2]. Outpatient treatment with BLENREP monotherapy demonstrated a profound and durable response and a manageable safety profile in the pivotal DREAMM-2 trial [3,4].

Multiple myeloma (MM), which belongs to the B-cell lymphomas, forms about 10% of all hematologic malignancies [5]. Existing treatment options have allowed prolongation of overall survival (OS) of MM patients in recent years, but the emergence of resistant clones still frequently leads to treatment failure. With each subsequent treatment, the depth and duration of response reduce; a proportion of patients become refractory to proteasome inhibitors (PIs), immunomodulators (IMIDs), and monoclonal antibodies. These patients have limited treatment options and, with a median OS of 5.6 months, a poor prognosis [6]. This reflects the urgent need for new therapeutic options with innovative mechanism of action [6]. In the pivotal DREAMM-2 trial, the BCMA*-targeted antibody-drug conjugate belantamab mafodotin (BLENREP) demonstrated a good and durable response in heavily pretreated, multiple refractory patients, especially as measured by the extent of pretreatment [3,4,7].

Profound and sustained response under BLENREP in the DREAMM-2 study.

In the multicenter, open-label, two-arm phase II DREAMM-2 trial, 97 patients whose disease was progressive after ≥3 lines of therapy received 2.5 mg/kg BLENREP every 3 weeks as monotherapy until disease progression or unacceptable toxicity [3,4]. The overall response rate (ORR), which was assessed by an independent committee, was the primary endpoint and was 32% (31/97; 97.5% CI: 21.7-43.%–43,6%) after a median 13-month follow-up [4]. The majority (18/31; 58%) of these responders benefited from a very good partial remission (VGPR†: n=11) or an even more profound response (CR‡, sCR‡; n=7). Secondary endpoints included median duration of response (mDOR; 11 months [95% CI: 4.2-NE]) and expected median OS (13.7 months [95% CI, 9.9 months-not reached]) in the overall population. The response and survival of patients with risk-associated cytogenetics or renal insufficiency was comparable to the results of the overall population [4].

Monitoring for corneal changes

The most common adverse events with 2.5 mg/kg BLENREP were keratopathy (72%, severity ≥3 in 46%) and thrombocytopenia (38%, severity ≥3 in 22%). Corneal side effects led to treatment delay in 47% of patients but to permanent treatment discontinuation in only 3%. After 13 months, visual acuity changes had resolved in 82% of patients; no permanent visual loss was observed [4]. To monitor side effects, an ophthalmologic examination is performed before starting treatment with BLENREP and before the first three subsequent cycles. Patients should also avoid contact lenses and regularly use preservative-free tear substitutes. Once corneal side effects occur, adjust the dosage of BLENREP or delay treatment [1]. Although dose modifications (delays or reductions) were frequently used for adverse event management in this study, they had minimal impact on response under BLENREP [4].

Conclusion

BLENREP has been approved in Switzerland since June 2022 and will be reimbursed by health insurers since November 2022 if the limitatio is met [1,2]. BLENREP is approved as monotherapy for the treatment of MM in heavily pretreated adult patients with at least four prior therapies who showed disease progression during the last therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulator, and one anti-CD38 monoclonal antibody [1]. Patients with a high degree of pre-treatment in particular can therefore now benefit from the effective and tolerable new treatment option.

* BCMA = B cell maturation antigen, surface protein exclusively present on myeloma cells and plasma cells

† VGPR = very good partial response

‡ CR = complete response; sCR=stringent complete response.

Literature:

Current professional information BLENREP®, www.swissmedicinfo.ch.
www.spezialitätenliste.ch. Last accessed: November 2022.
Lonial S et al: Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. The lancet oncology 2020; 21(2): 207-221.
Lonial S et al: Longer term outcomes with single-agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13-month follow-up from the pivotal DREAMM-2 study. Cancer 2021; 127(22): 4198-4212.
Moreau P et al: Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017; 28(suppl_4): iv52-iv61.
Gandhi UH et al: Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. Leukemia 2019; 33(9): 2266-2275.
Trudel S et al: Targeting B-cell maturation antigen with GSK2857916 antibody-drug conjugate in relapsed or refractory multiple myeloma (BMA117159): a dose escalation and expansion phase 1 trial. Lancet Oncol 2018; 19(12): 1641-1653.

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Brief technical information BLENREP®:

Blenrep (powder for concentrate for solution for infusion) W: belantamab mafodotin. I: Monotherapy for the treatment of multiple myeloma in adult patients who have already received at least 4 lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulator, and one anti-CD38 monoclonal antibody and who showed disease progression during the last therapy. Efficacy and safety in patients with prior BCMA-directed CART cell therapy has not been studied. D: 2.5 mg/kg body weight as an intravenous infusion every 3 weeks. See SmPC for recommended dose adjustments due to adverse effects. KI: Hypersensitivity to an ingredient. W/V: Adverse corneal effects have been observed. Ophthalmologic examinations should be performed prior to initiation of treatment, prior to subsequent 3 cycles of treatment, and during the course of treatment if clinically indicated. Application of a preservative-free tear substitute recommended. Thrombocytopenia events have been reported. A CBC should be requested prior to initiation of treatment and, if clinically indicated, during treatment. Infusion reactions and cases of pneumonitis have been observed. See SmPC for recommended course of action for Grade 2 or higher. IA: No formal studies conducted. S/S: Women of childbearing potential should use an effective method of contraception from the start of therapy until 4 months, and men with partners of childbearing potential should use an effective method of contraception from the start of therapy until 6 months after the last dose. Pregnancy and lactation: No data. Blenrep must not be used during pregnancy unless treatment with Blenrep is required due to the woman’s clinical condition. Women should be advised to wean before starting therapy with Blenrep and not to breastfeed until 3 months after the last dose. UW: Very common: pneumonia, upper respiratory tract infections, thrombocytopenia, anemia, neutropenia, keratopathy, events of blurred vision, events of dry eye, photophobia, nausea, diarrhea, vomiting, fever, fatigue, elevated aspartate aminotransferase, elevated gamma-glutamyltransferase, infusion-related reactions. Common: lymphopenia, leukopenia, eye irritation, increased creatine phosphokinase. Occasional: keratitis, albuminuria. Unknown: Pneumonitis. P: 100 mg vial. AK: A. Date of information: June 2022. GlaxoSmithKline AG, 3053 Münchenbuchsee. For detailed information, please visit www.swissmedicinfo.ch. Please report adverse drug reactions at pv.swiss@gsk.com. Professionals can request the above references from GlaxoSmithKline AG. This drug is subject to additional monitoring. For more information, see Blenrep Technical Information at www.swissmedicinfo.ch.