During COMy 2020, Multiple Myeloma Hub Steering Committee Member Paul Richardson, Dana-Farber Cancer Institute, Boston, US, spoke to the Multiple Myeloma Hub about advances in the novel, peptide-conjugated alkylator, melphalan flufenamide (melflufen).

Melflufen has been successful in overcoming resistance to standard chemotherapeutics as well as novel agents, such as proteasome inhibitors and immunomodulatory drugs. The high lipophilicity of melflufen facilitates rapid entry into myeloma cells. Furthermore, its alkylating activity is initiated by aminopeptidases, which are often overexpressed by myeloma cells, making the agent particularly selective. As a result, melflufen is better tolerated, with fewer off-target effects than its predecessor, melphalan.

Here, Paul Richardson discusses the major findings from preclinical studies and topline data from ongoing clinical trials evaluating melflufen for the treatment of multiple myeloma.

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During the American Society of Clinical Oncology (ASCO) Annual Meeting, the Multiple Myeloma Hub was pleased to speak to Katja Weisel, University Cancer Center Hamburg, Hamburg, DE. In this podcast she discusses the quadruplet combination of isatuximab with carfilzomib, lenalidomide and dexamethasone for the treatment of high-risk newly diagnosed multiple myeloma.

In this podcast, Katja Weisel describes the interim results of the phase II GMMG-CONCEPT trial including deep and durable responses, measurable residual disease negativity, remissions, and overall survival of the first 50 patients enrolled. She also discusses the trial design, including the cytogenetic features that classify patients as high risk, as well as the safety profile and dosing regimens.

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During the American Society of Clinical Oncology (ASCO) Annual Meeting, the Multiple Myeloma Hub was delighted to speak to Paul Richardson, Dana-Farber Cancer Institute, Boston, US. In this podcast he discusses cereblon E3 ligase modulators (CELMoDs) as a novel approach in the treatment of relapsed/refractory multiple myeloma.

Paul Richardson describes how preclinical data have shown CC-92480 to have potent and direct anti-myeloma and immunostimulatory effects. He discusses the results from the phase I, multicenter, international study that combined CC-92480 with dexamethasone in patients with relapsed and refractory multiple myeloma and describes the two dosing regimens (continuous and intensive), patient characteristics, and safety data. Dr Richardson also explains that the results show encouraging, durable responses, particularly for patients that have triple-refractory myeloma, which are a sub-group of patients where there is a significant clinical unmet need.

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During the 25th Congress of the European Hematology Association (EHA), the Multiple Myeloma Hub was pleased to speak to Saad Usmani, Levine Cancer Institute, Atrium Health, Charlotte, US. In this podcast he discusses data from three clinical trials, which address the use of quadruplet treatments and anti-BCMA therapy for multiple myeloma.

He describes the progression free survival, overall survival and safety profile of the 100 patients that were evaluable from the SWOG 1211 trial. This was a randomized, phase II trial, which evaluated lenalidomide, bortezomib and dexamethasone (RVd) induction followed by dose-attenuated RVd maintenance until disease progression with or without elotuzumab, in patients with high risk, newly diagnosed multiple myeloma.

He then talks about the dose escalation results of first-in-human trial of teclistamab, a BCMA bispecific antibody, in terms of overall response rates and safety profile. He then mentions the randomized phase III study looking at belantamab mafodotin in combination with RVd in patients with transplant ineligible newly diagnosed multiple myeloma.

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During COMy 2020, Nikhil Munshi, Dana-Farber Cancer Institute, Boston, US, spoke to the Multiple Myeloma Hub about genomics of high-risk MM.

Here, Nikhil Munshi highlights the positive shift in survival outcomes of patients with high-risk MM in recent years, owing to emerging treatments and diagnostic techniques. Three major points are discussed:

1. Who is high risk?

2. What are the characteristics of high-risk MM?

3. How do we treat patients with high-risk disease?

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During the 25th Congress of the European Hematology Association (EHA), the Multiple Myeloma Hub spoke to Steering Committee Member Heinz Ludwig, Wilhelminen Cancer Research Institute, Vienna, AT. This podcast outlines a study that aimed to determine the impact of the oral microbiome in patients uniformly treated with ixazomib + thalidomide + dexamethasone combination therapy for the treatment of relapsed/refractory MM.

Oral microbiome characteristics are highly heterogeneous between patients, and a higher microbiome diversity has been associated with favorable prognosis in patients with cancer. However, there remains a lack of data surrounding the influence of the oral microbiome on survival outcomes in patients with MM. This study sought to provide answers—listen for more information!

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During the American Society of Clinical Oncology (ASCO) Annual Meeting, the Multiple Myleoma Hub was pleased to speak to Adam Cohen, University of Pennsylvania, Philadelphia, US. In this podcast, he discussed the use of BFCR4350A, a novel bispecific FcRH5:CD3 T-cell engaging antibody, in patients with relapsed/refractory multiple myeloma.

Adam Cohen provides us with insights from pre-clinical data and explains the mechanism of action of BFCR4350A. He also describes the expression patterns of its target FcRH5, which make this drug less likely to have off-target effects and be specifically efficacious in patients with an amplification at the 1q21 locus. He also discusses the study design, criteria, and objectives of the phase I trial, including a step-up dosing regimen aimed to mitigate cytokine syndrome and neurotoxicity.

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During the American Society of Clinical Oncology (ASCO) Annual Meeting, the Multiple Myeloma Hub was pleased to speak to Nikhil Munshi, Dana-Farber Cancer Institute, Boston, US. In this podcast, he discusses the recent updates from the KarMMa phase II trial (NCT03361748). in patients with relapsed/refractory multiple myeloma.

Nikhil Munshi describes the mechanism of action of the idecabtagene vicleucel (ide-cel) BCMA targeting CAR T-cell therapy before detailing the study design. He then provides results from the 128 patients enrolled in the study, including and dose-response rates, overall response rates, complete response rates, and MRD negativity rates. He also describes the safety profile including cytokine release syndrome, neurotoxicity and cytopenias. These results demonstrate deep and durable responses for a heavily pre-treated patient population with relapsed/refractory multiple myeloma.

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During the American Society of Clinical Oncology (ASCO) Annual Meeting, the Multiple Myeloma Hub was pleased to speak to Jesus Berdeja, Sarah Cannon Research Institute, Nashville, US. In this podcast, he discusses the latest updates from the CARTITUDE-1. This was a phase I/IIb study of JNJ-4528, a B cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR T)-cell therapy in patients with relapsed/refractory multiple myeloma.

Jesus Berdeja begins by explaining the construct is different to other BCMA CAR T-cell constructs and then goes on to describe the study design, including patient characteristics and eligibility. He then describes the safety results from this study including the late onset of cytotoxic syndrome. He also discusses the overall response rate and measurable residual disease negativity.

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During the American Society of Clinical Oncology (ASCO) Annual Meeting, the Multiple Myeloma Hub was pleased to speak to Amrita Krishnan, City of Hope, Duarte, US. In this podcast, she discussed the phase I data of TAK-079, a novel anti-CD38 monoclonal antibody, in a heavily pre-treated population of patients with multiple myeloma.

She begins be describing the uniqueness of TAK-079 over other approved anti-CD38 antibodies and describes the mechanism of action. Amrita Krishnan then begins to discuss the promising safety and tolerability results including no infusion-related reactions and no significant lymphopenia or thrombocytopenia.

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