Clinical Lymphoma, Myeloma & Leukemia, Vol.22, Suppl.2 - October 2022

Abstracts Clinical Lymphoma, Myeloma & Leukemia October 2022 S336 (NCT04603495). Keywords: MPN, epigenetics, myelofibrosis, ruxolitinib, pelabresib, BET, Trial-in-Progress MPN-379 Matching-Adjusted Indirect Comparison (MAIC) of Pelabresib (CPI-0610) in Combination With Ruxolitinib vs. JAK Inhibitor Monotherapy in Patients With Intermediate or High-Risk Myelofibrosis Vikas Gupta PhD 1 , John Mascarenhas MD 2 , Marina Kremyanskaya MD, PhD 2 , Raajit K Rampal MD, PhD 3 , Moshe Talpaz MD 4 , Jean-Jacques Kiladjian MD, PhD 5 , Alessandro Vannucchi MD 6 , Srdan Verstovsek MD, PhD 7 , Gozde Colak PhD 8 , Debarshi Dey MD, PhD 9 , Claire Harrison MD, FRCP, FRCPath 10 1 Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada. 2 Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 3 Memorial Sloan Kettering Cancer Center, New York, NY, USA. 4 University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA. 5 Hôpital Saint-Louis, Université de Paris, Paris, France. 6 Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy. 7 University of Texas MD Anderson Cancer Center, Houston, TX, USA. 8 Constellation Pharmaceuticals, a MorphoSys Company, Boston, MA, USA. 9 MorphoSys AG, Planegg, Germany. 10 Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom Co n text: Pelabresib (CPI-0610) combined with ruxolitinib showed encouraging spleen and symptom responses in Janus kinase inhibitor (JAKi)-naïve patients with intermediate or high-risk myelofibrosis in Arm 3 of the Phase 2 MANIFEST study (NCT02158858). Cross-trial comparisons with JAKi monotherapy have limitations due to potential imbalances in baseline characteristics. Objecti v e: Matching-adjusted indirect comparison (MAIC) analysis was conducted to correct for potential imbalances in baseline characteristics, comparing primary (SVR35) and secondary (TSS50) endpoints at Week 24 for pelabresib and ruxolitinib (MANIFEST Arm 3) with JAKi monotherapy from Phase 3 studies (COMFORT-I and II, SIMPLIFY-1, and JAKARTA). Methods: Individual patient-level data were available for MANIFEST Arm 3 vs. only published summary data for the four comparator studies. Unanchored MAIC was conducted, adjusting for imbalances in gender, myelofibrosis subtype, International Prognostic Scoring System risk status, previous hydroxyurea use, platelet count, hemoglobin levels, spleen volume, and JAK2 V617F status. Weighted mean outcomes of treatment effects were estimated; weights were also used to calculate the effective sample size. Treatment effect outcomes for SVR35 and TSS50 are presented in terms of response rates (RRs) and response rate ratios (RRRs, RR in MANIFEST Arm 3/RR in comparator arm; RRR >1 favors MANIFEST Arm 3). Bias due to potential unmeasured differences in baseline characteristics cannot be excluded. Results: Complete summary-level balance in weighted distributions of prognostic factors was achieved. For SVR35 at Week 24, significant MAIC- adjusted RRRs (95% CI) were 1.5 7 (1.10–2.24; p=0.012), 1.82 (1.1 7 –2.83; p=0.008), 2.13 (1.51–3.02; p<0.0001), 2.26 (1.5 7 – 3.2 7 ; p<0.0001), 1. 7 6 (1.16–2.66; p=0.008) and 1.55 (1.06–2.2 7 ; p=0.023) for MANIFEST Arm 3 (pelabresib with ruxolitinib) versus COMFORT-I, COMFORT -II, SIMPLIFY-1 (ruxolitinib), SIMPLIFY-1 (momelotinib), JAKARTA (fedratinib 400 mg), and JAKARTA (fedratinib 500 mg), respectively, consistent with the significant results of unadjusted analyses. RRRs >1 were observed for TSS50 at Week 24 for all comparisons. Co n clusio n s: Results suggest that MAIC-adjusted improvements observed in SVR35 and TSS50 at Week 24 with pelabresib and ruxolitinib vs. ruxolitinib, fedratinib, or momelotinib monotherapy were consistent with unadjusted comparisons. Phase 3 MANIFEST-2 (NCT04603495), assessing pelabresib or placebo combined with ruxolitinib in JAKi- naïve patients with myelofibrosis, is ongoing. Keywords: MPN, SVR35, TSS50, ruxolitinib, fedratinib, momelotinib MPN-386 Real-World Ruxolitinib Treatment Pattern in Myelofibrosis Patients With Thrombocytopenia Sujan Kabir MD 1 , Jian Mei PharmD 1 , Yifei Wang PhD 2 , Natsumi Ichikawa PhD 3 , Suichi Ino PhD 3 , Claudia Lebedinsky MD 1 1 Sumitomo Pharma Oncology, Inc., Cambridge, USA. 2 Sumitovant Biopharma, New York, USA. 3 Sumitomo Pharma Co., Ltd, Osaka, Japan Backgrou n d: Ruxolitinib, the standard treatment for patients with myelofibrosis to reduce splenomegaly and improve myelofibrosis-associated symptoms, is associated with high rates of cytopenia effect. Thrombocytopenia, common in myelofibrosis patients, is associated with poor clinical outcomes, and its treatment confers a unique challenge. This real-world study characterized the disease and ruxolitinib treatment pattern in myelofibrosis patients with thrombocytopenia using US insurance claims data. Methods: Data from the IBM MarketScan ® Medicare Supplemental Database were retrospectively analyzed to identify patients aged  18 years with  1 claim for ruxolitinib and  2 non-diagnostic medical claims for myelofibrosis from 201 7 to 2019. The first ruxolitinib claim on or after the first myelofibrosis claim defined the index date. Patients who continuously enrolled in a health plan for 3 months before and 6 months after the index date were included. Clinical characteristics and ruxolitinib treatments were compared in myelofibrosis patients with or without a history of thrombocytopenia prior to ruxolitinib initiation. Results: Overall, 136 myelofibrosis patients who received ruxolitinib treatment were included in the analysis. The median age was 61 years, 61% were male, 62% had primary myelofibrosis, and 38% had post-polycythemia vera or essential thrombocythemia myelofibrosis. Prior to ruxolitinib treatment, 5 7 % of patients had a diagnosis of splenomegaly, 56% had anemia, 25% had thrombocytopenia, 19% had received RBC transfusion, and 7 % had