- Phase 2 and 3 Trials in Myeloma
- Novel Targets and Amyloid
- Treatment of NDMM and amyloidosis patients
- Immune Therapy for Multiple Myeloma
653. Myeloma and Plasma Cell Dyscrasias: Clinical-Prospective Therapeutic Trials: Phase 2 and 3 Trials in Myeloma
Jacob P. Laubach, Jonathan L. Kaufman, Douglas W. Sborov, et al.
The addition of DARA resulted in RVd induction and consolidation associated with ASCT after two years of maintenance therapy, followed by DARA plus R maintenance. Deep and sustained responses were also observed in patients with transplantable NDMM, including sCR and MRD negativity (10-5 and 10-6) rates. There were no new security concerns. These data support the use of D-RVd induction / consolidation and D-R maintenance in transplant eligible NDMM patients.
Kaz Groen, Claudia A.M. Stege, Kazem Nasserinejad, et al.
Intermediate fit patients benefit from the effective and feasible therapy combination ixazomib, daratumumab and dexamethasone, which improves their quality of life. However, discontinuation of treatment due to toxicity gives cause for concern: the entire treatment regimen is six percent, but especially only of ixazomib with eleven percent, or an incompliance that negatively affects progression-free survival.
Gordon Cook, Charlotte Pawlyn, Kara-Louise Royle, et al.
The study shows that the recruitment of older, less fitter patients for clinical trials is feasible. For more information see abstract.
Magaret Macro, Cyrille Touzeau, Clara Mariette, et al.
Ixazomib and daratumumab without dexamethasone have a favorable safety profile in this population of very elderly frail patients with RRMM. Almost a third of them had high-risk cytogenetic therapy.
Shaji K Kumar, Simon J Harrison, Michele Cavo, et al.
The addition of venetoclax to bortezomib and dexamethasone resulted in significantly improved progression-free survival, but increased mortality compared to Pbo in the general population. As in previous studies, venetoclax, in addition to bortezomib and dexamethasone, had the greatest improvement in progression-free survival in patients with t (11; 14) or high BCL2 with a favorable benefit-risk profile.
Herve Avet Loiseau, Pieter Sonneveld, Philippe Moreau, et al.
In the CASSIOPEIA study, D-VTd ind / ASCT / cons and daratumumab maintenance therapy showed the highest and most sustained MRD negativity rates. A reduced intensity (Q8W) of DARA maintenance therapy did not significantly improve MRD negativity compared to observation in patients treated with D-VTd. Although not long-lasting, daratumumab maintenance improved MRD negativity in patients treated with VTd.
653. Myeloma and Plasma Cell Dyscrasias: Clinical-Prospective Therapeutic Trials: Novel Targets and Amyloid
Suzanne Trudel, Adam D Cohen, Amrita Y. Krishnan, et al.
Cevostamab Mono continues to have clinically meaningful activity in heavily pretreated RRMM with a target dose-dependent increase in the ORR, but not an increase in the CRS rate. Persistent reactions are seen in patients with prior exposure to CAR-Ts, BsAbs, and ADCs. Compared to the SS dosage, the DS dosage at the 0.3 / 3.6 mg level appears to be associated with a trend towards an improved C1 safety profile.
Amrita Y. Krishnan, Monique C. Minnema, Jesús G. Berdeja, et al.
SC-talquetamab is well tolerated and highly effective in both RP2Ds. Rarer, higher doses of SC talquetamab (in the 800 µg / kg biweekly cohorts) did not negatively affect the safety profile described above.
Raymond Comenzo, Giovanni Palladini, Efstathios Kastritis, et al.
D-VCd has persistent clinical advantages over VCd in terms of haematological response and organ responses upon prolonged follow-up. However, it should be noted that many patients in the D-VCd arm received daratumumab monotherapy after 6 cycles of D-VCd. The patients in the VCd group, however, discontinued study treatment. Despite everything, the study continues to support the use of D-VCd versus VCd alone in newly diagnosed AL amyloidosis. D-VCd has now been approved and represents a new SOC for patients with AL amyloidosis.
Jeffrey A. Zonder, Joshua Richter, Naresh Bumma, et al.
REGN5458 further demonstrates an acceptable safety and tolerability profile with Gr 2 CRS in only 4.4% of patients and without Gr ≥ 3 CRS or neurotoxicity events. No new safety signals were observed. In multiple refractory patients with RRMM, an early, profound and sustained response rate of 73.3% was observed with the combined doses (96 & 200 mg).
Ajai Chari, Parameswaran Hari, Nizar J. Bahlis, et al.
Talazoparib plus daratumumab were well tolerated. The safety profile was comparable to that of the monotherapies. The combination showed promising efficacy in RRMM. The further clinical development of the combination therapy talazoparib plus daratumumab is therefore justified.
Sagar Lonial, Rakesh Popat, Cyrille Hulin, et al.
IBER + DEX showed promising and generally well-tolerated efficacy in heavily pretreated, triple exposed and refractory RRMM as well as when anti-BCMA therapy was administered beforehand; TEAEs could be managed with dose reductions and interruptions. This study supports the further development of IBER in MM, including phase 3 studies in combination therapies.
653. Myeloma and Plasma Cell Dyscrasias: Clinical-Prospective Therapeutic Trials; treatment of NDMM and amyloidosis patients
Hartmut Goldschmidt, Elias K Mai, Eva Nievergall, et al.
This phase III study demonstrates the superiority of MRD negativity rates after induction by adding a CD38 moAb to RVd. There were no increased SAE rates or premature discontinuation.
Aurore Perrot, Valérie Lauwers-Cances, Cyrille Touzeau, et al.
D-IRD is a safe option for extended induction before and as consolidation after ASCT. This treatment allows for a gradual deepening of the response in standard risk MM. 39.5 percent of the patients achieved an MRD negativity 10-6 after consolidation. The 2-year PFS was 95.2 percent and the 2-year OS was 100 percent. Compared to D-VTD or D-KRD, the MRD negativity rates are lower.
Martin F. Kaiser, Andrew Hall, Katrina Walker, et al.
The intensified Dara combination therapy before and after ASCT for UHiR NDMM and pPCLOPTIMUM demonstrated a clear PFS advantage over the MyXI procedure after 18 months. The authors of the study suggest that Dara-VRd is particularly effective in maintaining the response after ASCT.
Laura Rosinol, Albert Oriol, Rafael Ríos Tamayo, et al.
Timothy M. Schmidt, Prashant Kapoor, Susanna Joan Jacobus, et al.
See abstract for more info.
Jason Valent, Jeffrey A. Zonder, Michaela Liedtke, et al.
CAEL-101 demonstrates good tolerability as part of an AL amyloidosis treatment strategy and confirms previous results on the use of CAEL-101 in combination with anti-PCD.
653. Myeloma and Plasma Cell Dyscrasias: Clinical-Prospective Therapeutic Trials: Immune Therapy for Multiple Myeloma
Michael Sebag, Noopur S. Raje, Nizar J. Bahlis, et al.
Elranatamab Mono (Q1W or Q2W,) in RRMM had a manageable safety profile, exhibiting a confirmed ORR of 70 percent and a CR / sCR rate of 30 percent, with a confirmed ORR of 83 percent in RP2D. The authors consider it particularly important that elranatamab induces deep and sustained clinical responses in RRMM patients with / without prior targeted BCMA therapy. MRD evaluable patients even showed 100 percent MRD negativity. The data support continued development of elranatamab as a single agent and in combination with standard therapies.
Philippe Moreau, Saad Z. Usmani, Alfred L. Garfall, et al.
Teclistamab in the RP2D in 159 patients proved to be verifiably safe. The data also show that teclistamab monotherapy induces profound and lasting responses in heavily pretreated RRMM with a manageable safety profile.
Natalie S. Callander, Vincent Ribrag, Paul G. Richardson, et al.
Belamaf in combination with aICOS demonstrated encouraging clinical activity. The safety profile was easily manageable with dose adjustments in heavily pretreated RRMM.
Dan T. Vogl, Jonathan L. Kaufman, Sarah A. Holstein, et al.
Modakafusp alfa (TAK-573), a new candidate for the treatment of RRMM, demonstrated promising anti-myeloma activity in heavily pre-treated patients. This also applied to anti-CD38 mAb refractory patients and patients who had already received an anti-CD38 mAb.
David J. Chung, Nina Shah, Dina Stroopinsky, et al.
The investigation showed that successful site-specific production is possible. With the DC/MM fusion vaccination with lenalidomide maintenance vaccination after autoHCT, no significant increase in CR rates was achieved after 1 year, but measurable anti-MM immunoreactivity was observed. This calls for longer-term follow-up because of their effects on the duration of response.
Shaji K Kumar, Anita D'Souza, Nina Shah, et al.
TNB-383B in pts with RRMM is well tolerated with an ORR of 79% observed at doses ≥40 mg in the dose-escalation cohorts. Despite having a shorter follow-up period, this trend was also observed at doses ≥40 mg in the combined dose-escalation/expansion cohorts (ORR: 64%). Enrollment into the dose-expansion arm is ongoing; updated data will be presented at the meeting.
TNB-383B is well tolerated in patients with RRMM. Treatment achieved an ORR of 79 percent at doses ≥ 40 mg in the dose escalation cohorts. This trend was also evident at doses ≥ 40 mg in the combined dose escalation/expansion cohorts (ORR: 64%). Updated data will be presented in the oral session.