Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, clinical trials, MPN, Clinical Research, Chronic Myeloid Malignancies, Diseases, Therapies, therapy sequence, Myeloid Malignancies, Human
Methods: In the Phase 3 SIMPLIFY-1 study (S1), JAKi-naïve patients with MF (n=432) were randomized 1:1 to MMB or RUX. In SIMPLIFY-2 (S2), MF patients previously treated with RUX (n=156) were randomized 2:1 to MMB or best available therapy (BAT). For S2, taper and washout of active MF therapy was prohibited prior to randomization. RUX was included as BAT and 88.5% of S2 control arm received RUX. In both S1 and S2, following the 24-week (6 month) randomized treatment (RT) period, patients could continue MMB (MMB→MMB) and those randomized to RUX or BAT crossed over to open-label (OL) MMB (RUX/BAT→MMB) immediately without the need for tapering or washout.
Results: In S1, 197 patients transitioned from RUX→MMB at week 25, all of whom initiated MMB at the 200 mg daily dose with highly comparable dose intensity between MMB→MMB (171 patients) and RUX→MMB; 81% of the active patients were receiving 200 mg daily 12 weeks following crossover. Of note, over the 4 weeks prior to crossover, 71/197 (36%) patients were receiving an average RUX dose of ≤10 mg BID. At the first assessment following crossover to MMB, there was rapid improvement in mean Hgb (≈1 g/dL), and mean spleen volume was maintained (≈1700 cm3) post-crossover for both MMB→MMB and RUX→MMB patients (Figure 1). Furthermore, of the 92 RUX patients who were not TI responders at Week 24 (W24), 46% became TI responders 12 weeks after RUX→MMB. Of the 71 patients who received a mean of ≤10 mg BID RUX over the 4 weeks prior to crossover, only 10% achieved a spleen response (≥35% volume reduction from baseline) prior to W24 crossover. Post RUX→MMB, 23% achieved or maintained spleen response at Week 48.
Safety observations in S1 during the immediate 2‑week period following RUX→MMB revealed excellent tolerability; new onset Grade 3/4 anemia and thrombocytopenia were experienced by only 3% and 2% of patients respectively and there were no cases of RUX discontinuation syndrome. More broadly, all AE terms of any grade experienced within 2 weeks of RUX→MMB transition occurred at ≤7%. Weight gain associated with RUX was ~4-fold higher than that observed with MMB and did not further increase after cross-over.
Similar to S1, in S2 the crossover at W24 from BAT (mainly RUX) to MMB was associated with a rapid improvement in mean Hgb and stable or improved spleen volume.
MFSAF total symptom scores (TSS) were not collected during OL MMB treatment in S1 or S2; however, S2 provided TSS data on 79 of the 102 patients randomized to MMB who received RUX until the day immediately prior to initiation of MMB. W24 TSS improved by ≥50% from pre-study baseline in 26% of MMB patients, including in 22% of those who were on RUX therapy pre-study, immediately prior to starting MMB.
Conclusion: MMB is a promising new therapy for MF, and data provide confidence in an immediate transition to MMB from RUX without washout or tapering, which is likely to rapidly improve anemia without compromising safety or control of symptoms and spleen. In addition, no withdrawal effects were noted following transition from RUX→MMB. Patients may be better served by timely transition to therapy able to improve anemia while maintaining or improving splenic and symptom responses.
Disclosures: Mesa: AOP: Consultancy; Genotech: Research Funding; Constellation Pharmaceuticals, Inc., a MorphoSys Company: Consultancy, Research Funding; Promedior: Research Funding; LaJolla Pharmaceutical: Consultancy; Sierra Oncology: Consultancy, Research Funding; CTI: Research Funding; Geron: Consultancy; Blueprint: Consultancy; Samus: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy; Celgene: Research Funding; Incyte: Consultancy, Research Funding; AbbVie: Research Funding; Roche: Consultancy; Novartis: Consultancy; Gilead: Research Funding; Imago: Research Funding. Verstovsek: Constellation Pharmaceuticals: Consultancy; Gilead: Research Funding; Novartis: Consultancy, Research Funding; ItalPharma: Research Funding; NS Pharma: Research Funding; Roche: Research Funding; Promedior: Research Funding; Genentech: Research Funding; PharmaEssentia: Research Funding; Protagonist Therapeutics: Research Funding; Incyte: Consultancy, Research Funding; CTI BioPharma Corp.: Research Funding; Celgene: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; Blueprints Medicines Corp.: Research Funding; AstraZeneca: Research Funding; Pragmatist: Consultancy. Gupta: Sierra Oncology: Consultancy; BMS Celgene: Consultancy, Honoraria, Other: Participation on a Data Safety or Advisory board; Pfizer: Consultancy, Other: Participation on a Data Safety or Advisory board; Novartis: Consultancy, Honoraria; Roche: Other: Participation on a Data Safety or Advisory board; AbbVie: Consultancy, Other: Participation on a Data Safety or Advisory board; Constellation Pharmaceuticals, Inc., a MorphoSys Company: Consultancy, Honoraria. Giraldo: Takeda: Consultancy, Honoraria; Acindes: Consultancy, Honoraria; Alexion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; ZeroLMC Foundation: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria. Kiladjian: Incyte: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; AOP Orphan: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Oh: Sierra Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Geron: Consultancy, Membership on an entity's Board of Directors or advisory committees; Disc Medicine: Consultancy, Membership on an entity's Board of Directors or advisory committees; CTI BioPharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Constellation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgne/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kartos: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy; Cogent: Consultancy. Devos: Alexion: Honoraria, Speakers Bureau; Novartis: Consultancy; BMS/Celgene: Honoraria, Speakers Bureau; Morphosys: Consultancy; Incyte: Consultancy. Passamonti: BMS: Consultancy, Research Funding; Novartis: Consultancy; Celgene: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Sierra Oncology: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Roche: Consultancy; AOP Orphan: Consultancy; Karyiopharma: Consultancy; Kyowa Kirin and MEI: Consultancy; Novartis: Honoraria. Vannucchi: Roche: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Geron: Membership on an entity's Board of Directors or advisory committees; Blueprint: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kawashima: Sierra Oncology: Current Employment. Huang: Sierra Oncology: Current Employment. Strouse: Sierra Oncology: Current Employment. Harrison: Gilead: Membership on an entity's Board of Directors or advisory committees; Geron: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; EHA: Other: Leadership role; Janssen: Membership on an entity's Board of Directors or advisory committees; Sierra: Honoraria; MPN voice: Other: Leadership role; Constellation Pharmaceuticals, Inc., a MorphoSys Company: Membership on an entity's Board of Directors or advisory committees, Research Funding; Galacteo: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau; AOP Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Promedior: Membership on an entity's Board of Directors or advisory committees; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees; Keros: Consultancy; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Galecto: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings, Research Funding.
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