ABSTRACT
The phase 3 MOMENTUM study (NCT04173494) of the ACVR1/JAK1/JAK2 inhibitor momelotinib (MMB) vs. danazol (DAN) in patients with myelofibrosis (MF) previously treated with a JAK inhibitor (JAKi) met the primary endpoint and all key secondary endpoints at week 24 (W24). We provide updated results from week 48 assessments. Eligible patients had primary or post-ET/ PV MF;DIPSS high, Int-2, or Int-1 risk;Total Symptom Score (TSS) >=10;haemoglobin (Hb) <10 g/dL;platelets >=25 x 109/L;prior JAKi for >=90 days (>=28 days if red blood cell [RBC] transfusions >=4 units in 8 weeks or grade 3/4 thrombocytopenia/anaemia/ hematoma);and palpable spleen >=5 cm. Randomisation was 2:1 to MMB 200 mg/day or DAN 600 mg/day for 24 weeks, followed by open-label (OL) MMB. Week 48 endpoints included durations of response (TSS, transfusion independence [TI], splenic) and overall and leukaemia-free survival (OS, LFS). As of 17 May 2022, 93/130 (72%) MMB -> MMB and 41/65 (63%) DAN -> MMB patients received OL MMB;mean MMB durations were 48 weeks and 24 weeks, respectively. Analyses for W24 responders showed the following: of TSS responders, 31/32 (97%) MMB -> MMB and 6/6 DAN -> MMB patients had TSS < baseline;of TI responders, 36/40 (90%) and 10/13 (77%) had no RBC transfusions or Hb <8 g/dL;and of spleen responders, all patients had splenic volume < baseline. In the OL phase, the most common grade >=3 treatment-emergent adverse events (TEAEs) were thrombocytopenia (MMB -> MMB, 9%;DAN -> MMB, 15%) and anaemia (MMB -> MMB, 9%;DAN -> MMB, 2%). Grade >=3 infections occurred in 19% of MMB -> MMB and 10% of DAN -> MMB patients, including grade >=3 (nonfatal) COVID-19. Peripheral neuropathy (PN) occurred in 2% of patients in each arm, and none discontinued MMB due to PN. TEAEs led to MMB discontinuation in 18% (MMB -> MMB) vs. 10% (DAN -> MMB). A trend towards improved OS up to W24 was previously observed with MMB vs. DAN (hazard ratio [HR], 0.506;p = 0.0719);after all patients crossed over to OL MMB, OS and LFS curves for both arms converged (HR, 0.945, 95% CI, 0.528-1.693;HR, 0.830, 95% CI, 0.473-1.4555). Sixty of 81 (74%) MMB -> MMB and 29 of 43 (67%) DAN -> MMB patients with baseline platelets <=150 x 109/L entered the OL phase. Efficacy and safety results in thrombocytopenic subgroups in the OL period were consistent with the intent-to- treat (ITT) population. OL MMB maintained symptom, TI, and spleen responses with continued good survival and safety in the ITT and low platelet populations. MMB may address an unmet need in anaemic patients with MF.
ABSTRACT
Introduction: Despite several studies, the impact of coronavirus disease 2019 on patients with multiple myeloma remains uncertain. Material(s) and Method(s): We performed a survey that covered the period of the first and second waves of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in 23 centers inseven countries. Out of 352 patients with myeloma and SARS-CoV-2, 23% died. Results/Conclusions: Logistic regression showed a lower risk of death among patients treated with proteasome inhibitor and a higher risk of death for those who had a severe or a very severe course of disease.Copyright © 2023 Sciendo. All rights reserved.
ABSTRACT
Background: Proteasome inhibitors (PIs) & monoclonal antibodies are backbones of RRMM treatment;Ixa is approved with lenalidomide-dex for pts with ≥1 prior therapy, & Dara is approved in various regimens, including with bortezomib-dex (DVd). In CASTOR (DVd vs Vd), Vd was limited to 8 cycles;however, prolonged PI therapy is associated with improved outcomes. The IDd regimen with oral Ixa may enable longer-term PI therapy than with DVd. We evaluate IDd using a treat-to-progression approach. Methods: Ixa/Dara-naive RRMM pts receive Ixa 4 mg (days 1, 8, 15), Dara 16 mg/kg (days 1, 8, 15, 22, cycles 1–2;days 1, 15, cycles 3–6;day 1, cycles 7+), & dex 20 mg (days 1, 2, 8, 9, 15, 16, 22, 23) in 28-day cycles. The primary endpoint is ≥ very good partial response (VGPR) rate;secondary endpoints include overall response rate (ORR), progression-free survival (PFS), time to progression (TTP), overall survival (OS), & safety. We report data from the 2nd IA, conducted after ~50% of PFS events had occurred (data cutoff: 1/1/2021). Results: 61 pts were enrolled (median age 69 y, 19.7% aged ≥75 y;19.7% International Staging System stage III;26.2% high-risk cytogenetics [del(17p), t(4;14), t(14;16)], 42.6% expanded high-risk cytogenetics [high-risk &/or amp1q21]);59.0/26.2/14.8% of pts had received 1/2/3 prior lines. At data cutoff, pts had received a median of 16 IDd cycles;37.7% were ongoing. Relative dose intensity (RDI) of Ixa, Dara, & dex was 20%) TEAEs were diarrhea (39.3%), anemia (27.9%), thrombocytopenia (26.2%), & fatigue (21.3%);common (>5%) G≥3 TEAEs were pneumonia (11.5%), thrombocytopenia (11.5%), & anemia (8.2%). Infections & Infestations TEAEs were seen in 57.4% of pts (G≥3 24.6%) and were serious in 26.2%, including pneumonia (9.8%) and COVID-19/pneumonia (4.9%). Rate of peripheral neuropathy (PN) was 18.0% (1.6% G≥3). PN was 28.6% & 12.5%in pts with & without history of PN, respectively. Study drug dose modifications, reductions & discontinuations due to TEAEs were required in 57.4% (Ixa 36.1%, Dara 34.4%, dex 41.0%), 32.8%, & 9.8%of pts, respectively. Four pts died on study due to sudden death, COVID-19 pneumonia, septic shock, & COVID-19 (none were considered study drug-related). Conclusion: These IA data suggest IDd has a positive risk-benefit profile in RRMM pts, with a ≥VGPR rate of 30.5%, median PFS of 17.0 m, & a low rate of discontinuation due to TEAEs. The final analysis of this ongoing study is expected in 2022.