In this video, Paul Richardson, MD, Dana-Farber Cancer Institute, Boston, MA, discusses findings from the DETERMINATION trial (NCT01208662) evaluating the use of lenalidomide, bortezomib, and dexamethasone versus high-dose treatment with autologous stem cell transplantation (autoSCT) in patients with multiple myeloma. Dr Richardson first highlights some results from this trial, including the progression-free survival (PFS) observed in patients and the importance of transplant in controlling event-free survival (EFS). Dr Richardson then discusses the toxicities observed and further highlights other therapies changing the myeloma treatment landscape, including quadruplet therapies, monoclonal antibodies, CAR-T therapy, and bispecific T-cell engagers (BiTEs). This interview took place at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting in Chicago, IL.
Richard D. Kim, MD, Moffitt Cancer Center, Tampa, FL, presents data from the phase Ib KEYNOTE-651 trial (NCT03374254), which assessed pembrolizumab with modified FOLFOX7 or FOLFIRI in patients with metastatic colorectal cancer (mCRC). In two out of five cohorts, patients with microsatellite stable CRC were given first- or second-line pembrolizumab with modified FOLFOX7 or FOLFIRI and the progression-free survival (PFS) was found to be comparable to that of patients not receiving pembrolizumab. Dr Kim additionally discusses the efficacy of certain biomarkers such as PD-L1 levels and the mutational status of KRAS in patients. This interview took place at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting in Chicago, IL.
In this video, Francesco Forconi, MD, DM, PhD, FRCPath, University of Southampton, Southampton, UK, discusses genetic drivers in chronic lymphocytic leukemia (CLL), drawing focus on somatic hypermutations of the IgHV genes, and how to approach treatment in these patients. First, Dr Forconi explains the process of the development of this mutation in CLL, and further discusses the poorer outcome and shorter progression-free survival (PFS) associated with IgHV-unmutated patients compared to IgHV-mutated patients. Dr Forconi then goes on to discuss the important role that Bruton’s tyrosine kinase (BTK) and BCL2 inhibitors have played in improving outcomes for IgHV-unmutated patients, as well as the importance of using data from clinical trials to guide treatment combinations in the future. This interview took place at the 62nd Annual Scientific Meeting of the British Society for Haematology (BSH) 2022, in Manchester, UK.
Saad Usmani, MD, MBA, FACP, Memorial Sloan Kettering Cancer Center, New York, NY, gives an update on the CARTITUDE-5 study (NCT04923893), which compares the efficacy of bortezomib, lenalidomide and dexamethasone (VRd) induction therapy followed by ciltacabtagene autoleucel (cilta-cel) or lenalidomide and dexamethasone maintenance (Rd) in patients with newly diagnosed multiple myeloma (NDMM) who are transplant-ineligible or that have deferred transplantation until first relapse. The primary endpoint is measurable residual disease (MRD) negativity and secondary endpoints include overall response rate (ORR) and overall survival (OS). The results from this trial are eagerly awaited and could potentially be practice-changing. This interview took place at the Transplantation & Cellular Therapy (TCT) Meetings of ASTCT™ and CIBMTR® 2022 in Salt Lake City, Utah.
Karthik Ramasamy, MBBS, MRCP, FRCPath, PhD, Oxford University Hospitals NHS Foundation Trust, Oxford, UK, discusses how maintenance therapy has improved outcomes for patients with multiple myeloma and the benefit this brings for patients in the UK. Dr Ramasamy briefly mentions data from the Myeloma XI study (NCT01554852), which has shown that lenalidomide maintenance improves progression-free survival (PFS) and overall survival (OS) in patients. Dr Ramasamy then discusses patients with high-risk disease who do not obtain durable remissions with lenalidomide maintenance, and the need to find combination treatments for these patients, which is currently being investigated in the RADAR trial (ISRCTN46841867). This interview took place at the 62nd Annual Scientific Meeting of the British Society for Haematology (BSH) 2022, in Manchester, UK.
In this video, Sally Moore, MD, Royal United Hospital, Bath, UK, discusses some updates on the use of carfilzomib, lenalidomide and dexamethasone (KRd) in patients with multiple myeloma at first relapse in a real-world setting. Dr Moore gives an overview on the efficacy of this regimen, including prolonged progression-free survival (PFS) and deepening of responses, as well as the toxicities associated with KRd treatment. This interview took place at the 62nd Annual Scientific Meeting of the British Society for Haematology (BSH) 2022, in Manchester, UK.
Maximilian Merz, MD, Leipzig University, Leipzig, Germany, Roswell Park Comprehensive Center Institute, Buffalo, NY, comments on the management of patients with multiple myeloma not eligible for transplant, where a paradigm shift has been observed after the introduction of CD38 antibodies to upfront therapy, with higher rates of progression-free survival (PFS) and overall survival (OS) and long-lasting remissions. Data from the ALCYONE (NCT02195479) and MAIA (NCT02252172) trials led to the approval of several combinations of daratumumab, with a notable outcome improvement in elderly and frail patients. Dr Merz considers that the standard of care should point to antibody plus lenalidomide-dexamethasone (Rd) or bortezomib-melphalan-prednisone (VMP), but more data on quadruplet therapy for ineligible patients is needed. This interview took place at the 48th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT) 2022, which was held virtually.
Paul Richardson, MD, Dana-Farber Cancer Institute, Boston, MA, gives an update on the long-term results of the TOURMALINE-MM2 trial comparing ixazomib-lenalidomide-dexamethasone (IRd) to placebo-lenalidomide-dexamethasone (pbo-Rd) in patients with relapsed/refractory (R/R) multiple myeloma (NCT01850524). The results of this study showing a significantly improved progression-free survival (PFS) in patients treated with IRd led to the approval of ixazomib in the relapsed/refractory (R/R) setting. Long-term subgroup analysis revealed that an improved quality of response over time was correlated with better patient outcomes and suggests that treatment with ixazomib should be prolonged over an extended period of time to maximize benefits. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Peter Voorhees, MD, Levine Cancer Institute, Charlotte, NC, updates us on the findings from the Phase II GRIFFIN trial assessing the addition of daratumumab to lenalidomide-bortezomib-dexamethasone (D-RVd) versus lenalidomide-bortezomib-dexamethasone (RVd) alone in patients with newly diagnosed multiple myeloma (NCT02874742). By the end of two years of maintenance therapy, the complete response (CR) rate was 79.8% in the D-RVd group vs 60.8% in the RVd group. Measurable residual disease (MRD) negativity and sustained MRD negativity were also significantly higher in the D-RVd arm. Interestingly, the rates of MRD negativity increased significantly from the end of the first year of maintenance therapy to the second year of maintenance therapy. Moreover, although the data is still premature and statistical significance for progression-free survival (PFS) has not yet been reached, there is a trend towards improved PFS in the daratumumab arm. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Peter Voorhees, MD, Levine Cancer Institute, Charlotte, NC, outlines the results of a subgroup analysis of the GRIFFIN trial (NCT02874742) investigating the efficacy of the addition of daratumumab to lenalidomide-bortezomib-dexamethasone (D-RVd) in patients with multiple myeloma with high-risk cytogenetics. Dr Voorhees explains that adding 1q21 gain to the high-risk markers defined by IMWG criteria increases the study’s power which allows determining whether daratumumab provides a significant benefit to this patient population. After incorporating patients with 1q21 gain to the subgroup analysis, the study reported a trend towards an improved progression-free survival (PFS) for high-risk patients treated with D-RVd compared to RVd alone. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Surbhi Sidana, MD, Mayo Clinic, Stanford, CA, discusses the role of stem cell transplantation (SCT) in multiple myeloma, highlighting data from key clinical trials. The benefit of upfront SCT has been shown on multiple occasions and notably in the IFM 2009 trial (NCT01191060), which demonstrated that upfront transplant led to deeper measurable residual disease (MRD) negativity and longer progression-free survival (PFS). In addition, the FORTE trial comparing carfilzomib plus lenalidomide plus dexamethasone (KRd) followed by autologous stem cell transplantation (ASCT) and maintenance therapy versus KRd alone followed by maintenance therapy showed a superior PFS for both standard and high-risk patients undergoing early transplant. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Julia Driessen, MBBS, University of Amsterdam, Amsterdam, The Netherlands, shares the findings from a study aiming to investigate the effect of brentuximab vedotin addition to salvage chemotherapy compared to chemotherapy alone on progression-free survival (PFS), overall survival (OS), and complete metabolic response (CMR) rate prior to autologous stem-cell transplant (ASCT) in patients with a first relapse or primary refractory (R/R) classical Hodgkin lymphoma. Results demonstrated that the addition of brentuximab vedotin to salvage chemotherapy followed by ASCT increased PFS in relapsed but not in primary refractory patients. This finding suggests that other treatment strategies such as checkpoint inhibitors should be considered in chemotherapy-resistant patients. An increase in OS for the brentuximab vedotin cohort was also observed. Additionally, the study confirmed the prognostic value of pre-ASCT CMR for PFS and b-symptoms, stage, and primary refractory disease as prognostic factors for PFS and pre-ASCT CMR. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.