原创 菠萝西瓜 BioArtMED 2024-06-15 14:30 四川
Written by丨Pineapple and watermelon
Patients with multiple myeloma are initially treated with a triple or quadruple combination of proteasome inhibitors, immunomodulators, and anti-CD38 monoclonal antibodies. However, the majority of patients progress after initial therapy, highlighting the need for effective second-line combination therapies with new therapies. B-cell maturation antigen (BCMA) is an established target for the treatment of multiple myeloma. Belantamab mafodotin is an antibody-drug conjugate (ADC) targeting BCMA with multiple mechanisms of antitumor activity.
2024年6月1日，来自西班牙Hospital Universitario de Salamanca的María-Victoria Mateos教授与GSK公司携DREAMM-7临床团队The New England Journal of Medicine杂志上发表文章Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma。 在这项临床试验中报告了DREAMM-7试验的结果，该试验评估了Belantamab mafodotin、硼替佐米和地塞米松（BVd）与达雷木单抗、硼替佐米和地塞米松（DVd）相比对复发或难治性多发性骨髓瘤患者的疗效和安全性。 与DVd疗法相比，BVd疗法在复发或难治性多发性骨髓瘤患者接受至少一线治疗后，在无进展生存期方面具有显著优势。 大多数患者出现3级或更高级别的不良事件。
Trial design: This is an ongoing Phase 3, open-label, global randomized trial in patients with multiple myeloma who have received at least one line of therapy and who have progressed on or after the most recent treatment. Patients will be excluded from the trial if they have disease that is resistant to anti-CD38 therapy or have received anti-BCMA therapy. Patients are randomized in a 1:1 ratio to receive either BVd or DVd. Both treatment groups received bortezomib (subcutaneously at a dose of 1.3 mg/m2 body surface area, 21 days as days 1, 4, 8, and 11 of a cycle) and dexamethasone (oral or intravenous at a dose of 20 mg, on the day and the day after bortezomib administration) in the first 8 cycles. The BVd group received belantamab mafodotin (intravenously at a dose of 2.5 mg/kg body weight for 21 days in a 21-day cycle [every 3 weeks]) until disease progression. The dose of belantamab mafodotin can be reduced to 1.9 mg/kg or postponed to control adverse events. The DVd group was treated with daratumumab (16 mg/kg intravenously weekly in cycles 1 to 3, every 3 weeks in cycles 4 to 8, and every 4 weeks in cycles 9 and thereafter) until disease progression. Treatment is continued until disease progression, unacceptable toxic effects, withdrawal of informed consent, or death (whichever occurs first).
Clinical Endpoint: The primary endpoint is progression-free survival, defined as the time from randomization to the occurrence of documented disease progression or death due to any cause. Key secondary endpoints were overall survival, duration of response, and minimal residual disease (MRD)-negative status, the latter assessed by sequencing with a sensitivity of 10−5 or less. Other secondary endpoints were adverse events (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0) and ocular examination findings (graded using the Kerapathy and Visual Acuity (KVA) scale).
Trial results: A total of 494 patients were randomly assigned to receive either BVd (243 patients) or DVd (251 patients). At a median follow-up of 28.2 months, median progression-free survival was 36.6 months in the BVd arm and 13.4 months in the DVd arm (HR, 0.41; P<0.001). At 18 months, the overall survival rate was 84% in the BVd group and 73% in the DVd group. Analysis of the restrictive mean duration of response showed that BVd was superior to DVd (P<0.001). Twenty-five percent of patients in the BVd group and 10 percent of patients in the DVd group had a complete response or better with a negative MRD. Grade 3 or higher adverse events occurred in 95% of patients in the BVd group and 78% in the DVd group. Ocular events were more common in the BVd group than in the DVd group (79% vs. 29%); Such events can be managed with dose adjustments, and vision deterioration events have mostly been resolved.
As a result, BVd therapy has a significant advantage over DVd therapy in progression-free survival in patients with relapsed or refractory multiple myeloma after receiving at least one line of therapy. Most patients experienced grade 3 or higher adverse events. (This clinical trial is funded by GSK; DREAMM-7 ClinicalTrials.gov number NCT04246047; EudraCT number is 2018-003993-29)
2024年6月2日，来自希腊雅典国立卡波蒂斯坦大学（National and Kapodistrian University of Athens）医学院的Meletios Athanasios Dimopoulos教授与GSK公司携DREAMM-8临床团队在The New England Journal of Medicine杂志上发表文章Belantamab Mafodotin, Pomalidomide, and Dexamethasone in Multiple Myeloma。 在本临床试验中报告了DREAMM-8试验的结果，该试验评估了Belantamab mafodotin、泊马度胺和地塞米松（BPd）与泊马度胺、硼替佐米和地塞米松（PVd）的疗效。 对于接受来那度胺治疗的复发或难治性骨髓瘤患者，BPd在无进展生存期以及更深、更持久的缓解方面比PVd具有显著更大的优势。 其中眼部副作用事件很常见，但可以通过调整Belantamab mafodotin剂量来控制。
Trial design: This is an ongoing, open-label, global phase 3 randomized trial in patients with relapsed or refractory myeloma who have received at least one line of therapy, including lenalidomide, and who have progressed on or after the most recent treatment. Patients were randomized in a 1:1 ratio to receive either BPd or PVd. Patients in the BPd group were treated with 28-day cycles of Belantamab mafodotin (2.5 mg/kg body weight intravenously on day 1 of cycle 1 and 1.9 mg/kg intravenously on cycle 2 and day 1 thereafter) in combination with pomalidomide and dexamethasone. The dose of belantamab mafodotin can be delayed or reduced to control adverse events. Patients in the PVd group were treated with bortezomib in 21-day cycles (1.3 mg/m2 body surface area subcutaneously on days 1, 4, 8, and 11 of cycles 1 to 8 and 1 and subcutaneously on days 1 and 8 of cycles 9 and thereafter) in combination with pomalidomide and dexamethasone. Treatment continues until disease progression, unacceptable adverse effects, withdrawal of consent, or death (whichever occurs first).
Clinical Endpoint: The primary endpoint is progression-free survival, defined as the time from randomization to the earliest date of disease progression based on independent review committee assessment or death from any cause. Key secondary endpoints included overall survival, minimal residual disease (MRD) negative status, and duration of response. Other secondary endpoints included adverse events (including ocular adverse events), graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Results: A total of 302 patients were randomized; 155 were assigned to the BPd group and 147 to the PVd group. At a median follow-up of 21.8 months, the 12-month estimated progression-free survival rate was 71% in the BPd group compared with 51% in the PVd group (HR, 0.52; P<0.001). Overall survival data are immature. The percentage of patients who responded to treatment (partial response or better) was 77% in the BPd group and 72% in the PVd group; Complete remission or better was achieved in 40% and 16% of patients, respectively. Grade 3 or higher adverse events occurred in 94% of patients in the BPd group and 76% of patients in the PVd group. Ocular events occurred in 89% of patients in the BPd group and 30% in the PVd group; Ocular events in the BPd group were managed by adjusting the dose of Belantamab mafodotin. Nine percent of patients in the BPd group discontinued treatment due to ocular events, compared with those in the PVd group.
As a result, BPd has a significantly greater advantage over PVd in terms of progression-free survival and deeper, more durable responses in patients with relapsed or refractory myeloma treated with lenalidomide. Ocular side effect events are common but can be controlled by adjusting the dose of Belantamab mafodotin. (This clinical trial is funded by GSK; DREAMM-8 ClinicalTrials.gov NUMBER NCT04484623; EudraCT number is 2018-00434-21)
Original link: https://doi.org/10.1056/NEJMoa2405090
https://doi.org/10.1056/NEJMoa2403407