Hematologic Malignancies—Plasma Cell Dyscrasia

Kwee Yong, Marquita Camilleri, William Wilson, et al.
The study authors conclude, that In newly diagnosed multiple myeloma patients KCd consolidation was non-inferior to ASCT when receiving carfilzomib-cyclophosphamide-dexamethasone (KCd) induction and carfilzomib maintenance. High-risk patients had inferior outcomes, that were not influenced by ASCT or consolidation randomization. Clinical trial information: NCT02315716
Martin F. Kaiser, Andrew Hall, Katrina Walker, et al.
The study authors conclude, that this is the first report on a trial for ultra high-risk (UHiR) newly diagnosed multiple myeloma and plasma cell leukemia investigating Dara-CVRd induction and augmented ASCT. High Response rates were observed in this difficult-to-treat patient population. Toxicity was comparable to other induction regimens. But according to the authors, some early progressions stress the need for innovative approaches to UHiR NDMM. Clinical trial information: NCT03188172
Francesca Gay, Roberto Mina, Delia Rota-Scalabrini, et al.
The study authors conclude, that carfilzomib-lenalidomide-dexamethasone induction/consolidation with ASCT (KRd_ASCT) and carfilzomib-lenalidomide maintenance are highly effective in standard risk and also in single high-risk and double-hit patients, with impressive 4-year progression-free survival (PFS) from diagnosis (KRd_ASCT: HiR 62%, DH 55%) and 3-year PFS from maintenance (KR: HiR 69%, DH 67%). This supports their use in single high-risk patients. Clinical trial information: NCT02203643
Efstathios Kastritis, Vaishali Sanchorawala, Giampaolo Merlini, et al.
The study authors conclude, that updated results from the ANDROMEDA study reinforce the clinical superiority of DARA-VCd over VCd in patients with newly diagnosed AL amyloidosis and represent a new standard of care in AL amyloidosis. Clinical trial information: NCT03201965
Philippe Moreau, Pieter Sonneveld, for the CASSIOPEIA Study Investigators; 
The study authors observed a clinical benefit of daratumumab maintenance in transplant-eligible newly diagnosed multiple myeloma patients. Progression-free survival for daratumumab vs observation was significantly longer. With current follow-up, maintenance PFS benefit appeared only in pts treated with VTd asinduction/consolidation. Patients who received D-VTd induction/consolidation with or without daratumumab maintenance achieved similar progression-free survival; daratumumab significantly increased deeper response and MRD negativity rates vs observation. Daratumumab was well-tolerated without new safety signals. Clinical trial information: NCT02541383
Saad Zafar Usmani, Jesus G. Berdeja, Deepu Madduri, et al.
The study authors conclude, that a single infusion of cilta-cel yielded early, deep, and durable responses in heavily pretreated patients with multiple myeloma. There was a manageable safety profile at the recommended phase 2 dose. Further investigations in other MM populations in earlier lines of therapy and in outpatient settings are running. Clinical trial information: NCT03548207
Nizar J. Bahlis, Noopur S. Raje, Caitlin Costello, et al.
The study authors conclude, that the humanized bispecific monoclonal antibody Elranatamab had a manageable safety profile. subcutaneous dosing (≥215μg/kg) achieved an ORR of 75% with CR/sCR rate of 30%. This demonstrates the safety and efficacy of subcutaneous elranatamab in this relapsed/refractory population and supports the ongoing development of the drug for patients with multiple myeloma as monotherapy and combined with other therapies. Clinical trial information: NCT03269136
Amrita Y. Krishnan, Alfred L. Garfall, Maria-Victoria Mateos, et al.
The study authors conclude, that the BCMA × CD3 bispecific IgG4 antibody Teclistamab that redirects CD3+ T cells to BCMA-expressing multiple myeloma cells at the recommended phase 2 dose (weekly 1500 µg/kg SC) was well-tolerated. The treatment showed encouraging efficacy with durable, deepening responses.  This supports further investigation as monotherapy and in combination with other agents. With the extended exposure profile at the recommended phase 2 dose and delayed and low-grade cytokine release syndrome observed with subcutaneous administration, alternative subcutaneous dosing strategies are being explored. Clinical trial information: NCT03145181.
Jesus G. Berdeja, Amrita Y. Krishnan, Albert Oriol, et al.
Talquetamab (JNJ-64407564) is a bispecific IgG4 antibody that redirects T cell killing to MM cells. The study authors conclude, that at the recommended phase 2 dose (weekly 405 µg/kg SC), talquetamab showed a high clinical response rate. The treatment was well-tolerated in patients with relapsed/refractory multiple myeloma. Other SC dosing strategies are being explored. The study results support monotherapy development and combination approaches with this novel agent. Clinical trial information: NCT03399799