Sundar Jagannath, MD
More than 5000 abstracts are slated to be presented at the upcoming 2018 ASH Annual Meeting. Ahead of the conference, multiple myeloma experts Sundar Jagannath, MBBS, and Ajai Chari, MD, selected the most pivotal abstracts in their field.Updated analysis of a phase I, open-label study of LCAR-B38M, a chimeric antigen receptor T-cell therapy directed against B-cell maturation antigen, in patients with relapsed/refractory multiple myeloma (Abstract 955)
The ongoing, first-in-human LEGEND-2 trial of bispecific LCAR-B38M CAR T-cell therapy (NCT03090659) demonstrated a promising overall response rate (ORR) and a manageable safety profile in patients with relapsed/refractory multiple myeloma. Results showed an ORR of 88%; the complete response (CR) rate was 74%, the very good partial response (VGPR) rate was 4%, and the partial response (PR) rate was 11%.
Among those who achieved CR, 39 out of 42 patients were minimal residual disease (MRD) negative. Additionally, the median duration of response (DOR) was 16 months; for those who achieved a CR, the median DOR was 22 months. The median progression-free survival (PFS) for all patients was 15 months (95% CI, 11–not reached) and 24 months for those who achieved a CR (95% CI, 15-NR). Median overall survival (OS) was not reached. A phase I/II study of this therapy is now ongoing (NCT03548207).
This is one of several abstracts being presented at this year’s meeting on CAR T-cell therapy, said Jagannath, a professor of Medicine, Hematology, and Medical Oncology at Mount Sinai Health System.
“[We will get updates on CAR T-cell therapy—newer CAR T-cell therapies,” added Jagannath. “We will get to hear about [bispecific T-cell engagers] antibodies, bispecific antibodies. [Researchers] will be able to show that these are working very well.”Results of the pivotal STORM study (part 2) in penta-refractory multiple myeloma (MM): deep and durable responses with oral selinexor plus low dose dexamethasone in patients with penta-refractory mm (Abstract 598)
Selinexor, a novel SINE compound that blocks XPO1, is being explored in an additional cohort of 122 patients with penta-refractory multiple myeloma in part 2 of the STORM trial—part 1 of which enrolled patients with both quad- and penta-refractory disease.
Prior results were presented at the 2018 SOHO Annual Meeting, which demonstrated that the combination of selinexor and dexamethasone demonstrated promising clinical activity in patients with penta-refractory multiple myeloma, a population that currently has no standard-of-care regimen. The data showed that the doublet regimen was associated with an ORR of 26.2% and a median OS of 8.6 months in patients with penta-refractory disease.
In these updated data, an independent review committee determined the ORR was 26.2%, with a 6.5% VGPR rate, including 2 stringent CRs (sCRs). Two patients who relapsed on CAR T-cell therapy achieved PRs. Additionally, the clinical benefit rate was 39.3%, and 79% of patients achieved stable disease. The median DOR, PFS, and OS were 4.4 months, 3.7 months, and 8.0 months, respectively.
“We are getting follow-up results from selinexor, which is a new drug that is in front of the FDA,” said Jagannath. “That is really important.”Efficacy and updated safety analysis of a safety run-in cohort from GRIFFIN, a phase II randomized study of daratumumab (Dara; Darzalex), bortezomib (V; Velcade), lenalidomide (R; Revlimid), and dexamethasone (D; Dara‐Vrd) versus Vrd in patients (Pts) with newly diagnosed (ND) multiple myeloma (MM) eligible for high‐dose therapy (HDT) and autologous stem cell transplantation (ASCT; Abstract 151).
This GRIFFIN analysis is one of a number of daratumumab (Darzalex)-based regimens being explored in the newly diagnosed multiple myeloma setting. In this ongoing, multicenter, open-label, active-controlled, randomized trial, investigators sought to determine whether the addition of daratumumab to VRd followed by HDT, ASCT, and consolidation VRd would be tolerable and further induce responses.
Results showed that the overall safety profile of this combination was consistent with those previously reported for the agents alone, with a manageable toxicity and no new safety findings reported. Data showed that the investigator-assessed VGPR or better rate was 100% and the sCR plus CR rate following consolidation therapy was 63%.
“Here will be many of the long-term follow-up [studies] on combination therapy, with the use of daratumumab in upfront combinations,” said Jagannath. “People will be excited to know if daratumumab could be effectively used in newly diagnosed myeloma patients with great results. This year, also, will be a stellar year in the ASH meeting for myeloma.”