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DREAMM-3: Belantamab Mafodotin Did Not Meet Primary Endpoint
Belantamab mafodotin did not significantly improve PFS, when compared to pomalidomide plus low-dose dexamethasone, in patients with relapsed or refractory MM in the phase 3 DREAMM-3 trial (ClinicalTrials.gov Identifier: NCT03525678).3
The trial included 325 patients with MM who had received at least 2 prior lines of therapy, including lenalidomide and a proteasome inhibitor. The patients were randomly assigned to receive belantamab mafodotin (n=218) or pomalidomide and dexamethasone (n=107). The median follow-up was 11.5 months in the belantamab mafodotin arm and 10.8 months in the pomalidomide-dexamethasone arm.
The incidence of AEs, serious AEs, and grade 3-4 AEs was generally similar between the arms. Severe neutropenia and infections were more common with pomalidomide-dexamethasone, while severe thrombocytopenia and ocular AEs were more common with belantamab mafodotin.
The median PFS was 11.2 months in the belantamab mafodotin arm and 7.0 months in the pomalidomide-dexamethasone arm (HR, 1.03; 95% CI, 0.72-1.47; P =.558).
The overall response rate was 41% in the belantamab mafodotin arm and 36% in the pomalidomide-dexamethasone arm. The rate of very good partial response or better was 25% and 8%, respectively. The rate of complete response or better was 10% and 3%, respectively.
The median duration of response was not reached in the belantamab mafodotin arm and was 8.5 months in the pomalidomide-dexamethasone arm.
Though belantamab mafodotin did not improve PFS in this analysis, the longer duration of response suggests that belantamab mafodotin may improve PFS at a later time point, said study presenter Katja Weisel, MD, of the University Medical Center of Hamburg-Eppendorf in Germany.
OS data were not mature, but the median OS was similar between the arms. The median OS was 21.2 months in the belantamab mafodotin arm and 21.1 months in the pomalidomide-dexamethasone arm.
“I think most of us do believe that, even though it was not superior in this study, [belantamab mafodotin is] still a very active agent and will likely prove itself in a different context,” Dr Mikhael said. “But it’s a reminder that we set a high bar for drugs to be approved, and we’ll have to wait now until we have more concrete data.”
Belantamab mafodotin was granted accelerated approval in the US in 2020 but was pulled from the market in 2022 because results from this trial did not meet requirements to support the drug’s continued approval.6,7
However, belantamab mafodotin is still under development. It is being investigated in combination regimens and in earlier lines of therapy, Dr Weisel said.
RedirecTT-1: First Results With Bispecific Antibody Combo
The combination of teclistamab and talquetamab appeared safe and effective in patients with relapsed or refractory MM in the phase 1/2 RedirecTT-1 trial.4
“This is the first time results of 2 bispecifics used in combination have ever been reported in hematologic malignancies,” said study presenter Yael C. Cohen, MD, of Tel-Aviv Sourasky (Ichilov) Medical Center and Sackler School of Medicine at Tel Aviv University in Israel. She noted that talquetamab targets GPRC5D and CD3, and teclistamab targets BCMA and CD3.
Dr Cohen presented results for 93 patients treated with teclistamab and talquetamab in this ongoing trial (ClinicalTrials.gov Identifier: NCT04586426). The patients had previously received treatment with a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.
Patients received varying doses of teclistamab and talquetamab, but 34 patients received the recommended phase 2 dose, which was teclistamab at 3 mg/kg and talquetamab at 0.8 mg/kg, each given every other week.
The median follow-up was 13.4 months for the entire cohort and 8.1 months for patients who received the recommended phase 2 dose.
“The safety profile of the combination was consistent with that of monotherapies, with no new or additive toxicities,” Dr Cohen said.
Treatment-emergent AEs occurred in 96.8% of all patients and 94.1% of those who received the recommended phase 2 dose. The rate of grade 3-4 AEs was 88.2% and 79.4%, respectively.
The rate of cytokine release syndrome was 76.3% overall and 73.5% in patients who received the recommended phase 2 dose. There were 5 immune effector cell-associated neurotoxicity syndrome events in 3 patients. Six patients died from a treatment-related AE, 1 of whom received the recommended phase 2 dose.
Dr Cohen noted that the overall response rate with teclistamab and talquetamab is similar to response rates seen with CAR T-cell therapies.
The overall response rate was 86.6% in the entire cohort and 96.3% in patients who received the recommended phase 2 dose. The complete response rates were 40.2% and 40.7%, respectively. The median duration of response was not reached in either group.
Among patients with extramedullary soft tissue plasmacytomas, the overall response rate was 85.7%. The median duration of response was not reached in this group, at a median of 7.2 months of follow-up.
In the overall cohort, the median PFS was 20.9 months. The median PFS was not reached in patients who received the recommended phase 2 dose. The 9-month PFS rate was 70.1% in the overall cohort and 77.1% in patients who received the phase 2 dose.
Dr Mikhael said this study is second on his list of exciting ASCO abstracts for a few reasons.
“One, because it demonstrates the feasibility of being able to combine these bispecifics together,” he said. “I think it was very reassuring that they can feasibly be given together. I think most striking was the response rate together. The theory of being able to leverage both targets — both BCMA and GPRC5D — is being fulfilled here. I think that also is very encouraging and exciting for us to see … because we’re seeing that high level of response without necessarily additional toxicity.”
Disclosures: The CARTITUDE-4 trial was supported by Janssen Research & Development and Legend Biotech. The DSMM XVII trial was partly supported by Amgen, Celgene, and Bristol Meyers Squibb. The DREAMM-3 trial was supported by GlaxoSmithKline. The RedirecTT-1 trial was supported by Janssen Research & Development.
Dr Mikhael disclosed relationships with Amgen, Bristol Meyers Squibb, Janssen, Karyopharm Therapeutics, Sanofi, and Takeda. The study presenters and some of their colleagues declared affiliations with various biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of their disclosures.
References
1. Dhakal B, Yong K, Harrison SJ, et al. First phase 3 results from CARTITUDE-4: Cilta-cel versus standard of care (PVd or DPd) in lenalidomide-refractory multiple myeloma. ASCO 2023. June 2-6, 2023. Abstract LBA106.
2. Knop S, Stuebig T, Kull M, et al. Carfilzomib, lenalidomide, and dexamethasone (KRd) versus elotuzumab and KRd in transplant-eligible patients with newly diagnosed multiple myeloma: Post-induction response and MRD results from an open-label randomized phase 3 study. ASCO 2023. June 2-6, 2023. Abstract 8000.
3. Weisel K, Hungria VTM, Radinoff A, et al. A phase 3, open-label, randomized study to evaluate the efficacy and safety of single-agent belantamab mafodotin (belamaf) compared to pomalidomide plus low-dose dexamethasone (Pd) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): DREAMM‑3. ASCO 2023. June 2-6, 2023. Abstract 8007.
4. Cohen YC, Morillo D, Gatt ME, et al. First results from the RedirecTT-1 study with teclistamab (tec) + talquetamab (tal) simultaneously targeting BCMA and GPRC5D in patients (pts) with relapsed/refractory multiple myeloma (RRMM). ASCO 2023. June 2-6, 2023. Abstract 8002.
5. Janssen submits supplemental biologics license application to U.S. FDA seeking approval of CARVYKTI® for the earlier treatment of patients with relapsed or refractory multiple myeloma. News release. PR Newswire. Published June 6, 2023. Accessed June 16, 2023.
6. FDA granted accelerated approval to belantamab mafodotin-blmf for multiple myeloma. News release. US Food and Drug Administration. Published August 6, 2020. Accessed June 16, 2023.
7. GSK provides an update on Blenrep (belantamab mafodotin-blmf) US marketing authorisation. News release. GSK. Published November 22, 2022. Accessed June 16, 2023.
This article originally appeared on Cancer Therapy Advisor
