Expert Predicts Immunotherapy Combos Will Transform Treatment in Multiple Myeloma
October 08, 2019 06:19pm
By Kristi Rosa
The upcoming 4th Annual Medical Crossfire Hematologic Malignancies, hosted by Physicians’ Education Resource, LLC, promises a lively exchange between experts in multiple myeloma, leukemia, and lymphoma and physician attendees who are on the front lines of patient care. This educational format moves away from didactic lectures and instead focuses on discussions on scientific advances and their impact on real-world patient cases.
Kenneth C. Anderson, MD
The upcoming4th AnnualMedical Crossfire®: Hematologic Malignancies, hosted by Physicians’Education Resource®, LLC, promises a lively exchange between experts in multiple myeloma, leukemia, and lymphoma and physician attendees who are on the front lines of patient care. This educational format moves away from didactic lectures and instead focuses on discussions on scientific advances and their impact on real-world patient cases.
The event takes place Saturday, July 11, 2020, in New York, New York. Panelists will discuss novel agents and chimeric antigen receptor (CAR) T-cell therapy in acute lymphocytic leukemia, use of genetic testing to deter­mine frontline treatment in chronic lymphocytic leu­kemia (CLL), evolving paradigms in multiple myeloma, and the latest developments in mantle cell lymphoma and diffuse large B-cell lymphoma (DLBCL).
“The conference provides the opportunity to probe the opinions of several different experts as to how they would manage, for example, a particular case of newly diagnosed or relapsed myeloma,” saidKenneth C. Anderson, MD, 1 of the 3 conference cochairs. Elias Jabbour, MD, of The University of Texas MD Anderson Cancer Center in Houston and Anas Younes, MD, of Memorial Sloan Kettering Cancer Center in New York, New York, are also cochairs.
Targeted Therapies in Oncologyspoke with Anderson to learn more about this exciting event.
“I think there’s a revolution in terms of novel therapies for hematologic malignancies that includes leukemias, lymphomas, and multiple myelomas,” said Anderson, program director of the Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma Therapeutics as well as the Kraft Family Professor of Medicine.
“We are seeing multiple new targeted agents; mul­tiple new immune agents, especially CAR T-cells and bispecific T-cell engagers; and unique combinations across all these cancer settings,” Anderson said. How these novel advances can be optimized to improve the outcomes for patients in a given setting will be dis­cussed during each Medical Crossfire® section across various hematologic malignancies.
Anderson will lend his considerable expertise, which spans from the late 1980s to the present day, during the conference’s multiple myeloma section. His research encompasses the advances involving immunomodu­latory drugs, proteasome inhibitors, and monoclonal antibodies, with a focus on both the tumor and the tumor microenvironment.
“Our work has resulted in the transformation of mul­tiple myeloma, leading to a 3- to 4-fold improvement in patient survival,” Anderson said. “Many patients undergoing maintenance therapy have transformed myeloma into a chronic illness and eventually grow old and die from something else.”
Anderson was one of the coinvestigators on the phase II trial leading to the FDA’s approval of bortezomib (Velcade).1The investigators observed a rate of response to bortezomib of 35% in 193 patients, including 7 in whom myeloma protein became undetectable and 12 in whom the protein was detectable only by immunofix­ation. Overall survival was 16 months, with a median duration of response (DOR) of 12 months. The discovery of how this proteasome inhibitor worked soon led to further breakthroughs, espe­cially in combinations involving other targeted therapies and chemotherapies.
The major trends in hematologic treatments over the past year involved developments with targeted therapies, immune therapies, and combination therapies, Anderson said. For tar­geted therapies, he noted the role of venetoclax (Venclexta), especially in patients who harbor t(11;14) and express high levels of BCL-2.2The targeted therapy is indicated for CLL or small lymphocytic leukemia and for patients with newly diagnosed acute myeloid leukemia in combination with azacitidine (Vidaza), decit­abine (Dacogen), or low-dose cytarabine.3
“On the immune side, there are BCMA [B-cell maturation antigen]directed immuno­toxins, bispecific T-cell engagers, and CAR T cells, all of which look promising in clinical trials,” Anderson said. “Rapid progress is being made in both the targeted and immune therapies areas.”
Patients with multiple myeloma have especially benefited from combination ther­apy, Anderson noted. In patients with newly diagnosed disease, the triplet combination of lenalidomide (Revlimid)/bortezomib/ dexamethasone, abbreviated as RVd, is used broadly and has achieved a very high rate of response and DOR.
Adding a monoclonal antibody such as dara­tumumab (Darzalex) to RVd resulted in deeper responses. During the 2019 American Society of Hematology (ASH) Annual Meeting, findings from the GRIFFIN trial demonstrated that adding daratumumab to RVd (D-RVd) in patients with newly diag­nosed multiple myeloma resulted in a stringent complete response (sCR) of 62.6%, compared with standard-of-care treatment RVd, for which sCR was 45.4%.4Adding the anti-CD38 antibody improved the likelihood of achieving sCR (OR, 1.98; 95% CI, 1.12-3.49;P= .0177).
The overall complete response (CR) rate (sCR + CR) also improved with D-RVd (79.8% vs 60.8%;P= .0045), and the proportion of patients achiev­ing minimal residual disease nega­tivity was twice as high with D-RVd. At 24 months, both regimens led to rates of progression-free survival (PFS) exceeding 85% and rates of overall survival (OS) exceed­ing 90%.
Similarly, in the relapsed/refractory setting, adding daratumumab to carfilzomib (Kyprolis) and dexamethasone reduced the risk of disease progression or death by 37% compared with carfilzomib and dexamethasone alone, accord­ing to findings from the phase III CANDOR trial presented at the 2019 ASH Annual Meeting.5
Investigators reported that the PFS was not yet reached with the addition of the anti- CD38 antibody daratumumab compared with 15.8 months with carfilzomib and dexameth­asone alone (HR, 0.63; 95% CI, 0.46-0.85;P= .0014). At a median follow-up of 17 months, the median OS had not yet been reached in either arm (HR, 0.75; 95% CI, 0.49-1.13;P= .08).
These advances will be the focus of further discussion during the4th AnnualMedical Crossfire®: Hematologic Malignancies. The con­ference’s innovative format provides the most practical and engaging educational forum in the field of hematologic malignancies. The far-reach­ing benefits of attending will give those present more confidence in providing personalized care for their patients.