Purpose. We examined the impact of diabetes and hyperglycemia on cancer-specific survival of patients with metastatic or recurrent breast cancer (BC). Methods. We performed a retrospective analysis of 265 patients with advanced BC receiving palliative chemotherapy. BC-specific mortality was compared for diabetic and nondiabetic patients as well as for patients that presented hyperglycemia during treatment. Results. No difference was observed between the diabetic and nondiabetic patients in terms of overall survival (OS). A difference in OS was observed between nondiabetic patients and diabetic patients who had hyperglycemia. The OS was greater in diabetic patients with proper metabolic control than diabetic patients with hyperglycemia. The risk of death was higher in patients with mean glucose levels >130 mg/dL during treatment. Several factors were associated with poor OS: tumor stage, hormone-receptor-negative tumors, HER2 negative disease, multiple metastatic sites, presence of visceral metastases, and mean glucose >130 mg/dL. Conclusion. Elevated glucose levels are associated with a poor outcome in diabetic and nondiabetic patients in contrast to patients with normoglycemic levels, conferring an elevated risk of death. According to these results, clinicians should monitor glucose levels during treatment for advanced breast cancer disease and take action to maintain normal glucose levels.

Persistent thrombocytopenia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Romiplostim and eltrombopag are the currently available thrombopoietin receptor agonists (TPO-RAs), and some studies with very small numbers of cases have reported their potential efficacy in the allo-SCT setting. The present retrospective study evaluated the safety and efficacy of TPO-RAs in 86 patients with persistent thrombocytopenia after allo-HSCT. Sixteen patients (19%) had isolated thrombocytopenia (PT), and 71 (82%) had secondary failure of platelet recovery (SFPR). TPO-RA therapy was started at a median of 127 days (range, 27 to 1177 days) after allo-SCT. The median initial and maximum administered doses were 50 mg/day (range, 25 to 150 mg/ day) and 75 mg/day (range, 25 to 150 mg/day), respectively, for eltrombopag and 1 mg/kg (range, 1 to 7 mg/kg) and 5 mg/kg (range, 1 to 10 mg/kg), respectively, for romiplostin. The median platelet count before initiation of TPO-RA therapy was 14,000/mL (range, 1000 to 57,000/mL). Platelet recovery to 50,000/mL without transfusion support was achieved in 72% of patients at a median time of 66 days (range, 2 to 247 days). Eighty-one percent of the patients had a decreased number of megakaryocytes before treatment, showing a slower response to therapy (P = .011). The median duration of treatment was 62 days (range, 7 to 700 days). Grade 3-4 adverse events (hepatic and asthenia) were observed in only 2% of the patients. At last follow-up, 81% of patients had discontinued TPO-RAs and maintained response, and 71% were alive. To our knowledge, this is the largest series analyzing the use of TPO-RAs after allo-SCT reported to date. Our results support the efficacy and safety in this new setting. Further prospective trials are needed to increase the level of evidence and to identify predictors of response.

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INTRODUCTION: The outcome of patients (pts) with R/R AML or MDS after failing HMA and/or BCL-2 inhibitor combinations is poor. CPX-351 (Vyxeos™) is a dual liposomal formulation of cytarabine and daunorubicin, at a fixed synergistic 5:1 molar ratio, approved by the US Food and Drug Administration (FDA) for the treatment of newly diagnosed therapy-related AML or AML with myelodysplastic related changes (AML MRC). GO (Mylotarg™) is a humanized immunoglobulin G4 antibody directed against CD33 and conjugated to the DNA toxin calicheamicin, also approved by the FDA for the treatment of newly diagnosed or R/R CD33-positive AML. We have hypothesized that the combination of CPX-351 and GO induces superior antitumor efficacy compared to either agent alone for this patient population. GOALS: To determine the safety and efficacy of CPX-351 in combination with GO in patients with R/R AML and post-HMA failure HR-MDS. METHODS: Here we present updated results of this single-arm, pilot study (NCT03672539) enrolling pts with CD33 positive R/R AML, post-HMA failure HR-MDS (>10% blasts). Pts received induction cycle CPX-351 (daunorubicin 44 mg/m 2 and cytarabine 100 mg/m 2) administered via intravenous (IV) infusion on days 1, 3, and 5. GO was administered at a dose of 3 mg/m 2 (capped at one 4.5 mg vial) IV on day 1. Pts not attaining complete remission (CR) or CR with incomplete count recovery (CRi) after 1 cycle, could receive a 2 nd induction cycle of CPX-351 at the same dose, but only on days 1 and 3 with GO 3 mg/m 2 on day 1. Pts attaining CR/CRi could receive up to 2 consolidation cycles, after a minimum of 4 weeks from the start of the last cycle with CPX-351 (daunorubicin 29 mg/m 2 and cytarabine 65 mg/m 2) IV on days 1 and 3 and GO at 3 mg/m 2 on day 1. GO was only administered during the second consolidation cycle if there was evidence of minimal residual disease (+MRD) as measured by flow cytometry. GO could also be administered as a single agent for maintenance treatment on day 1 every 6 weeks, in case of persistent detection of MRD. RESULTS: Twenty-four pts have been enrolled between November 2018 and April 2021. Patient characteristics are summarized in Table 1. Twenty-three pts were diagnosed with R/R AML, and 1 with HR-MDS. Eighteen (75%) pts had previously been treated with venetoclax in combinations with HMA's and/or chemotherapy . We observed an overall response rate (ORR) of 55% (n=13), including CR (n=4), CRi (n=4) and PR (n=5). Responses are summarized in Table 2. Among the eight-pts with CR/CRi, 4 were in an MRD negative remission. None of the pts transitioned to stem cell transplantation (SCT) due to age and comorbidities. One patient in CR after induction cycle was taken off the study on day 40 due to infection and concerns of myelosuppression during consolidation. This patient was transitioned to decitabine monotherapy and remains in remission. Three pts received 2 inductions courses, 5 pts received consolidation and 1 pts received GO maintenance. Among responders, the median time to ANC >0.5 x10 9/L was 46 days (30-101) and PLT >50 x10 9/L was 42 days (33-76), the median time to ANC >1 x10 9/L was 50 days (31-113) and PLT >100 x10 9/L was 42 days (34-104) after induction (Table 3). With a median follow-up of 24 months, the median OS was 5 months [95% CI 1.9-8] (Figure 2), and the median duration of response was 7 months [95% CI 0-9]. Adverse events regardless of causality (Table 4) were mainly due to infectious complications. There were no treatment-related grade 3-4 non-hematological toxicity. Thirty-day mortality was 8% (n=2); both pts died from complications of septicemia. Five additional pts (21%) died within 60 days of treatment, including 2 with progressive disease, 2 with persistent cytopenias and who withdrew care due to worsening performance status, and 1 whose family also withdrew care after the patient was found to have a large hemorrhagic left temporal lobe brain mass. CONCLUSION: The combination of CPX-351 and GO is feasible and continues to show activity with acceptable toxicities in this high-risk disease population. The presence of significant myelosuppression and infectious complications remain a challenge in patients treated with this regimen. Figure 1 Figure 1. Disclosures Kadia: Jazz: Consultancy; Genentech: Consultancy, Other: Grant/research support; Liberum: Consultancy; Amgen: Other: Grant/research support; Pulmotech: Other; Cure: Speakers Bureau; AbbVie: Consultancy, Other: Grant/research support; Dalichi Sankyo: Consultancy; BMS: Other: Grant/research support; Novartis: Consultancy; Pfizer: Consultancy, Other; Aglos: Consultancy; Sanofi-Aventis: Consultancy; Cellonkos: Other; Ascentage: Other; Genfleet: Other; Astellas: Other; AstraZeneca: Other. Faderl: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Sasaki: Pfizer: Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Research Funding. Short: Amgen: Consultancy, Honoraria; Jazz Pharmaceuticals: Consultancy; AstraZeneca: Consultancy; Takeda Oncology: Consultancy, Research Funding; Astellas: Research Funding; Novartis: Honoraria; NGMBio: Consultancy. Daver: Bristol Myers Squibb: Consultancy, Research Funding; Sevier: Consultancy, Research Funding; Gilead Sciences, Inc.: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Trillium: Consultancy, Research Funding; Glycomimetics: Research Funding; Novimmune: Research Funding; Amgen: Consultancy, Research Funding; FATE Therapeutics: Research Funding; Trovagene: Consultancy, Research Funding; Hanmi: Research Funding; Abbvie: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; ImmunoGen: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy, Other: Data Monitoring Committee member; Dava Oncology (Arog): Consultancy; Celgene: Consultancy; Syndax: Consultancy; Shattuck Labs: Consultancy; Agios: Consultancy; Kite Pharmaceuticals: Consultancy; SOBI: Consultancy; STAR Therapeutics: Consultancy; Karyopharm: Research Funding; Newave: Research Funding. DiNardo: AbbVie: Consultancy, Research Funding; Forma: Honoraria, Research Funding; Takeda: Honoraria; ImmuneOnc: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Notable Labs: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Agios/Servier: Consultancy, Honoraria, Research Funding; Foghorn: Honoraria, Research Funding; Celgene, a Bristol Myers Squibb company: Honoraria, Research Funding. Ferrajoli: Janssen: Other: Advisory Board ; BeiGene: Other: Advisory Board, Research Funding; AstraZeneca: Other: Advisory Board, Research Funding. Jabbour: Amgen, AbbVie, Spectrum, BMS, Takeda, Pfizer, Adaptive, Genentech: Research Funding. Konopleva: Eli Lilly: Patents & Royalties: intellectual property rights, Research Funding; Genentech: Consultancy, Honoraria, Other: grant support, Research Funding; Novartis: Other: research funding pending, Patents & Royalties: intellectual property rights; Sanofi: Other: grant support, Research Funding; Calithera: Other: grant support, Research Funding; Rafael Pharmaceuticals: Other: grant support, Research Funding; Forty Seven: Other: grant support, Research Funding; Stemline Therapeutics: Research Funding; Ablynx: Other: grant support, Research Funding; Agios: Other: grant support, Research Funding; Ascentage: Other: grant support, Research Funding; KisoJi: Research Funding; Reata Pharmaceuticals: Current holder of stock options in a privately-held company, Patents & Royalties: intellectual property rights; F. Hoffmann-La Roche: Consultancy, Honoraria, Other: grant support; Cellectis: Other: grant support; AstraZeneca: Other: grant support, Research Funding; AbbVie: Consultancy, Honoraria, Other: Grant Support, Research Funding. Andreeff: Daiichi-Sankyo: Consultancy, Research Funding; ONO Pharmaceuticals: Research Funding; Medicxi: Consultancy; Karyopharm: Research Funding; Novartis, Cancer UK; Leukemia & Lymphoma Society (LLS), German Research Council; NCI-RDCRN (Rare Disease Clin Network), CLL Foundation; Novartis: Membership on an entity's Board of Directors or advisory committees; Aptose: Consultancy; Oxford Biomedica UK: Research Funding; Glycomimetics: Consultancy; Breast Cancer Research Foundation: Research Funding; Senti-Bio: Consultancy; Amgen: Research Funding; AstraZeneca: Research Funding; Syndax: Consultancy; Reata, Aptose, Eutropics, SentiBio; Chimerix, Oncolyze: Current holder of individual stocks in a privately-held company. Kantarjian: Astra Zeneca: Honoraria; Aptitude Health: Honoraria; Pfizer: Honoraria, Research Funding; Ascentage: Research Funding; Immunogen: Research Funding; Precision Biosciences: Honoraria; Ipsen Pharmaceuticals: Honoraria; KAHR Medical Ltd: Honoraria; Amgen: Honoraria, Research Funding; Astellas Health: Honoraria; Novartis: Honoraria, Research Funding; Jazz: Research Funding; Daiichi-Sankyo: Research Funding; BMS: Research Funding; AbbVie: Honoraria, Research Funding; Taiho Pharmaceutical Canada: Honoraria; NOVA Research: Honoraria. Ravandi: Prelude: Research Funding; Jazz: Honoraria, Research Funding; Taiho: Honoraria, Research Funding; Astex: Honoraria, Research Funding; Xencor: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Syros Pharmaceuticals: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria, Research Funding; Agios: Honoraria, Research Funding. Alvarado: Daiichi-Sankyo: Research Funding; MEI Pharma: Research Funding; Astex Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Research Funding; CytomX Therapeutics: Consultancy; FibroGen: Research Funding; BerGenBio: Research Funding; Sun Pharma: Consultancy, Research Funding. OffLabel Disclosure: To determine the safety and efficacy of CPX-351 in combination with GO in patients with R/R AML and post-HMA failure HR-MDS.

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