denotes an abstract that is clinically relevant.
denotes that this is a recommended PHD Trainee Session.
denotes that this is a ticketed session.Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical Research, patient-reported outcomes, Diseases, survivorship, Myeloid Malignancies
Methods: Patients randomized to pacritinib 200 mg BID and to BAT on PERSIST-2 were included if they were alive and on study at the start of the week 12 efficacy assessment period. Survival was assessed by Total Symptom Score (TSS; v2.0 excluding tiredness) reduction at various thresholds (≥50%, ≥20%, ≥10%, >0%) and transfusion independence (TI) response. TI was assessed among patients who required red blood cell (RBC) transfusion at baseline (within 90 days) and was defined, for the purposes of a landmark survival analysis, as the absence of RBC transfusions over any 12-week period from first dose through week 14 (allowing for a ±2-week window around week 12). Overall survival (OS) was estimated via the K-M method following the landmark approach; survival in responders vs non-responders was compared using the log-rank test.
Results: Of the 59 patients treated with pacritinib who had a reduction of TSS≥10%, the median age was 67 years, 25% had a baseline high-risk DIPSS, median platelet count was 61 x109/L, median hemoglobin was 9.7 g/dL, and baseline TSS was 19.1. Reduction of TSS≥10% was associated with improved OS, with 1 death among 59 responders vs 4 deaths among 30 non-responders (hazard ratio [HR]=0.12, 95% confidence interval [CI]: 0.01, 0.79] P=0.021, Fig 1a). Similar to spleen volume reduction, the association between TSS response and OS weakened at more stringent TSS response thresholds (Fig 1c, e), with the BAT arm not showing an association between TSS response and OS at any threshold. (Fig 1b, d, f).
In order to assess the relationship of specific TSS domains and survival , a landmark OS analysis was performed based on ≥20% reduction in physical function scores (sum of ‘tiredness’ and ‘inactivity’), spleen-related symptom scores (sum of ‘abdominal discomfort’, ‘early satiety’, and ‘left rib pain’), and cytokine-related symptom scores (sum of ‘itching’, ‘night sweats’, and ‘bone pain’). For cytokine-related symptoms, the number of deaths in PAC responders was significantly different compared to non-responders, with 0 deaths among 35 responders vs 2 among 15 non-responders (P=0.0325). Conversely the deaths among responders (2/22) vs non-responders (2/20) were not significantly different in the BAT arm. For the physical function and spleen-related symptom subscales, no significant differences between PAC responders and non-responders was observed (HR=0.60; 95% CI [0.05, 6.74] P=0.679) and (HR=0.26; 95% CI 0.02, 2.93, P=0.2435) respectively.
Among 36 patients on PAC who received RBC transfusions at baseline, 7 achieved TI over at least a 12-week period up to the time of the landmark analysis. There were no deaths among TI responders compared to 2 (6.9%) among TI non-responders. There were too few TI responders on BAT (only 2 out of 38) to assess the impact on survival.
Conclusion: In cytopenic myelofibrosis patients enrolled in PERSIST-2, having a reduction of TSS≥10% on full-dose PAC was associated with OS benefit – a finding that has not been noted with other JAK inhibitors to date. By contrast, this association was not found with BAT, (82% of these patients received ruxolitinib). Thus, reductions in TSS in patients treated with PAC were associated with an OS benefit. It is possible that pacritinib, with its distinctive mechanism of action, may offer a unique survival advantage for MF patients with moderate or severe thrombocytopenia, and further studies are required to understand the potential mechanisms of these distinct clinical observations.
Study funded by CTI BioPharma Corp., a Sobi company.
Disclosures: Harrison: CTI: Honoraria, Speakers Bureau; Galecto: Honoraria, Speakers Bureau; GSK: Honoraria, Speakers Bureau; Morphosys: Honoraria, Speakers Bureau; AOP: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Speakers Bureau. Palandri: Novartis, BMS, Celgene, GSK, Amgen, AbbVie, Karyopharm, AOP, Sierra Oncology, Janssen: Consultancy, Honoraria. Mascarenhas: Bristol Myers Squibb, Celgene, CTI BioPharma, Geron, Incyte Corporation, Janssen, Kartos Therapeutics, Merck, Novartis, PharmaEssentia, Roche; Participated in consulting or advisory committees – AbbVie, Bristol Myers Squibb, Celgene, Constellation Pharmac: Research Funding; AbbVie, Bristol Myers Squibb, Celgene, CTI BioPharma, Geron, Incyte Corporation, Novartis, Janssen, Kartos Therapeutics, Merck, PharmaEssentia, Roche: Research Funding; Incyte, Novartis, Roche, Geron, GSK, Celgene/BMS, Kartos, AbbVie, Karyopharm, PharmaEssentia, Galecto, Imago, Sierra Oncology, Pfizer, MorphoSys, CTI Bio: Consultancy; Bristol Myers Squibb, Celgene, Constellation Pharmaceuticals/MorphoSys, CTI BioPharma, Galecto, Geron, GSK, Incyte Corporation, Karyopharm Therapeutics, Novartis, PharmaEssentia, Prelude Therapeutics, Pfizer, Merck, Roche, AbbVie, Kartos: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie, CTI BioPharma Corp, a Sobi company, Geron, GlaxoSmithKline, Imago, Incyte, Kartos, Kayropharm, MorphoSys, Novartis, Pfizer, PharmaEssentia, Sierra: Consultancy; GSK: Honoraria. Palmer: Incyte: Consultancy, Other: Money went to the institution; morphosys: Consultancy, Other: Money went to institution; Jubliant: Consultancy; Sierra Oncology: Consultancy, Other: Money went to Institution; CTI BioPharma Corp.: Consultancy, Honoraria, Other: Money went to institution. Gerds: Accurate Pharmaceuticals, Constellation Pharmaceuticals, CTI BioPharma, Imago BioSciences, Incyte Corporation, Kratos Pharmaceuticals: Research Funding; AbbVie, Bristol Myers Squibb, Constellation Pharmaceuticals, GlaxoSmithKline, Kartos, Novartis, PharmaEssentia, Sierra Oncology: Consultancy. Kiladjian: Incyte Corporation: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; AOP Orphan Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; AbbVie, AOP Health, Bristol-Myers Squibb, GlaxoSmithKline, Incyte, Novartis, Pharmaessentia.: Consultancy. Buckley: CTI BioPharma Corp., a Sobi company: Current Employment, Other: Company provided vested and unvested equity awards to author as a company employee as part of overall compensation package, and all such equity grants were subject to accelerated vesting and pay out following Company's sale to new ownership. Roman-Torres: CTI BioPharma Corp., a Sobi company: Consultancy, Other: Company provided vested and unvested equity awards to author as a company employee as part of overall compensation package, and all such equity grants were subject to accelerated vesting and pay out following Company's sale to new ownership. Rampal: Servier: Consultancy; Kartos: Consultancy; Dainippon: Consultancy; Constellation: Research Funding; Zentalis: Research Funding; Incyte: Research Funding; Morphosys/Constellation: Consultancy; Stemline: Research Funding; Sumitomo: Consultancy; Ryvu: Research Funding; Karyopharm: Consultancy; Zentalis: Consultancy; Pharmaessentia: Consultancy; Galecto: Consultancy; CTI BioPharma Corp: Consultancy; Celgene-BMS: Consultancy; GSK-Sierra: Consultancy; Incyte: Consultancy.
OffLabel Disclosure: Pacritinib is a kinase inhibitor indicated for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50x10^9/L. This indication is approved under accelerated approval based on spleen volume reduction. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
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