Citations 327

Ivosidenib (IVO) in Combination with Azacitidine (AZA) in Newly Diagnosed (ND) Older Patients with IDH1 R132-Mutated Acute Myeloid Leukemia (AML) Induces High Response Rates: A Phase 2 Sub-Study of the Beat AML Master Trial

Blood | November 23, 2021 | Volume: 138 | Issue: Supplement 1 | Pages: 875-875

10.1182/blood-2021-149115

Abstract Background: IVO is an oral potent inhibitor of mutated IDH1 (IDH1m) enzyme, recently approved for the treatment (Tx) of ND adult patients (pts) with IDH1m AML ≥75 years old or with comorbidities precluding use of intensive induction chemotherapy, and adult pts with relapsed or refractory AML. In this Phase 2 sub-study of the Beat AML Master Trial, we evaluated the efficacy of IVO + AZA combination Tx in ND pts aged ≥60 years with IDH1m AML (ClinicalTrials.gov: NCT03013998) Methods: This open-label multicenter (16 sites / 9 enrolling) combination Tx study enrolled ND pts with R132 mIDH1 AML, utilizing the modified minimax Simon's 2-stage Phase 2 design. Pts received IVO + AZA for 6 cycles in the absence of disease progression (PD), unacceptable toxicity or stem cell transplant. Pts who achieved complete remission (CR)/complete remission with hematologic improvement (CRh)/complete remission with incomplete hematologic recovery (CRi) continued IVO + AZA for a total of 12 cycles, then IVO monotherapy until PD. Pts without CR/CRh/CRi after 6 cycles continued IVO + AZA if they demonstrated Tx benefit, as defined in Figure 1. Key eligibility included ND IDH1 R132 mutated AML pts aged ≥60 years and ECOG performance status 0 - 2 (Karnofsky ≥60). All pts received IVO 500 mg/day orally in continuous 28-day cycles + AZA 75 mg/m2 IV or SC on days 1-7 every 28 days. The primary endpoint was CR+CRh+CRi rate after 6 cycles of Tx. Response was assessed using modified 2017 ELN AML criteria. The modified minimax Simon's 2-stage design required 40 pts and tested the null hypothesis that the CR/CRh/CRi rate equaled 25% vs the alternative of 50% (one-sided alpha = 0.025, power 90%). Stage 1 required >5/16 responses for continued enrollment. Even though these criteria were met, the sponsor decided to discontinue the trial on 12/12/2019. Here we report the final primary endpoint results. Data were frozen 02/03/2021. Results: Between 07/2018 and 11/2019, 19 patients were enrolled with IDH1m AML; 18 started IVO + AZA Tx and are included in the analyses. At data freeze, 5 pts had died and 7 pts still on Tx were offered standard of care IVO. Median age of the pts was 75 years, 50% were ≥75 years, 61% were female and 89% were White (Table 1). The most common reasons for Tx discontinuation were trial discontinued by sponsor (7 or 39%), stem cell transplant (4 or 22%), and PD (3 or 17%). A total of 13 pts achieved CR/CRh/CRi (72%) by up to 6 cycles of Tx (Table 2 & Figure 2). Over the entire study period, 14 pts achieved CR/CRh/CRi (78%) with 8 CR (44%), 3 CRh (17%) and 3 CRi (17%). No deaths occurred within the first 60 days of Tx. After a median follow up of 19.8 months (mos), Page 2 median response duration was not reached, with 12-mos disease-free survival rate of 69%; also, median OS was not reached, with 12- and 18-mos OS rates of 100% and 73%, respectively. The median (range) time on Tx was 12 mos (<1 - 26.6); 2 pts (11%) discontinued Tx due to an adverse event (AE) - 2 Grade 3 serious AEs (SAEs), differentiation syndrome and skin infection. Overall, 5 pts had 7 Tx-related SAEs; most common Tx-related SAE was differentiation syndrome in 4 pts (22%), of which 3 (17%) were considered Grade ≥3 (Table 3). The most common AEs of any grade (in ≥25% of pts) were diarrhea (61%), constipation (50%), nausea and hypokalemia (each 44%); and most common Grade ≥3 Tx-related AEs were differentiation syndrome and QTc prolongation (each 17%). The most common Tx-related laboratory abnormalities of any grade were decreased platelet count (22%) and decreased WBC count (17%). Conclusions: In ND pts with IDH1m AML and ≥60 years of age, IVO + AZA Tx was associated with a high CR/CRh/CRi rate, no early deaths (60 days) and a 1-year OS of 100%. IVO + AZA was acceptably tolerated and no unexpected toxicities occurred. Most common unique toxicities of IVO observed during the study were differentiation syndrome and QTc prolongation; these led to Tx discontinuation in only 1 pt. CR/CRh/CRi rate obtained with IVO +AZA is higher than that previously reported in studies with the individual agents or intensive chemotherapy approaches, suggesting a synergistic effect. Our overall response rate is similar to that reported recently for IVO + AZA in older ND IDH1 mutant AML pts, despite not including pts with morphologic leukemia-free state and partial remission. Based on these results, a global Phase 3 evaluation of IVO or placebo plus AZA is ongoing (NCT03173248). Figure 1 Figure 1. Disclosures Patel: BMS-Celgene, Agios: Membership on an entity's Board of Directors or advisory committees; Aptevo Therapeutics: Research Funding; Peerview: Honoraria. Ruppert: Telios Pharma: Consultancy. Borate: Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharma: Research Funding; Blueprint Medicine: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Rampal: Membership on an entity's Board of Directors or advisory committees; Galecto, Inc.: Consultancy; Promedior: Consultancy. Stein: Syros Pharmaceuticals, Inc.: Consultancy; Daiichi Sankyo: Consultancy; PinotBio: Consultancy; Celgene: Consultancy; Bristol Myers Squibb: Consultancy; Jazz Pharmaceuticals: Consultancy; Foghorn Therapeutics: Consultancy; Blueprint Medicines: Consultancy; Gilead Sciences, Inc.: Consultancy; Abbvie: Consultancy; Janssen Pharmaceuticals: Consultancy; Genentech: Consultancy; Agios Pharmaceuticals, Inc: Consultancy; Novartis: Consultancy; Astellas: Consultancy; Syndax Pharmaceuticals: Consultancy. Stock: Pfizer: Consultancy, Honoraria, Research Funding; amgen: Honoraria; agios: Honoraria; jazz: Honoraria; kura: Honoraria; kite: Honoraria; morphosys: Honoraria; servier: Honoraria; syndax: Consultancy, Honoraria; Pluristeem: Consultancy, Honoraria. Kovacsovics: AbbVie: Research Funding; Janssen Pharmaceuticals: Research Funding; Amgen Inc.: Research Funding; Novartis: Research Funding; Stemline: Honoraria; Jazz Pharmaceutials: Honoraria. Blum: Leukemia and Lymphoma Society: Research Funding; Nkarta: Research Funding; Celyad Oncology: Research Funding; Syndax: Honoraria; Xencor: Research Funding; Abbvie: Honoraria; Forma Therapeutics: Research Funding; AmerisourceBergen: Honoraria. Arellano: KITE Pharma, Inc: Consultancy; Syndax Pharmaceuticals, Inc: Consultancy. Schiller: Sangamo: Research Funding; Takeda: Research Funding; Ono-UK: Consultancy, Research Funding; Gamida Cell Ltd.: Research Funding; Tolero: Research Funding; Samus: Research Funding; Karyopharm: Research Funding; BMS/Celgene: Consultancy, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Amgen: Consultancy, Current equity holder in publicly-traded company, Honoraria, Research Funding, Speakers Bureau; Bio: Research Funding; Mateon: Research Funding; Genentech-Roche: Research Funding; FujiFilm: Research Funding; Agios: Consultancy, Research Funding, Speakers Bureau; Actinium Pharmaceuticals, Inc: Research Funding; Kite/Gilead: Honoraria, Research Funding, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Arog: Research Funding; Delta-Fly: Research Funding; Celator: Research Funding; Forma: Research Funding; Astellas: Honoraria, Research Funding, Speakers Bureau; Stemline Therapeutics, Inc.: Honoraria, Research Funding, Speakers Bureau; Regimmune: Research Funding; PrECOG: Research Funding; Constellation Pharmaceuticals: Research Funding; Trovagene: Research Funding; Elevate: Research Funding; Deciphera: Research Funding; Actuate: Research Funding; Jazz: Consultancy, Honoraria, Research Funding, Speakers Bureau; Daiichi-Sankyo: Research Funding; Onconova: Research Funding; Geron: Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Current equity holder in publicly-traded company, Research Funding; Abbvie: Research Funding; Sanofi: Honoraria, Research Funding, Speakers Bureau; Pharma: Consultancy; Johnson & Johnson: Current equity holder in publicly-traded company; Biomed Valley Discoveries: Research Funding; Eli Lilly: Research Funding; ASH foundation: Other: Chair-unpaid; Sellas: Research Funding; Ono: Consultancy; Incyte: Consultancy; Ariad: Research Funding; AstraZeneca: Consultancy; Kaiser Permanente: Consultancy; Cyclacel: Research Funding; MedImmune: Research Funding; Ambit: Research Funding; Leukemia & Lymphoma Society: Research Funding; Bluebird Bio: Research Funding; Boehringer-Ingleheim: Research Funding; Cellerant: Research Funding; CTI Biopharma: Research Funding; Janssen: Research Funding; Kura Oncology: Research Funding; Pharmacyclics: Honoraria, Speakers Bureau; Millennium: Research Funding; National Marrow Donor Program: Research Funding; NIH: Research Funding; Onyx: Research Funding; Pharmamar: Research Funding; UC Davis: Research Funding; UCSD: Research Funding; Evidera: Consultancy; NCI: Consultancy; Novartis: Speakers Bureau. Olin: Actinium: Honoraria; Abbvie: Honoraria; Amgen: Honoraria; Cellectis: Research Funding; Pfizer: Research Funding; Genentech: Research Funding; Daiichi Sankyo: Research Funding; Astellas: Honoraria, Research Funding. Foran: pfizer: Honoraria; gamida: Honoraria; servier: Honoraria; kura: Research Funding; abbvie: Research Funding; takeda: Research Funding; trillium: Research Funding; revolution medicine: Honoraria; novartis: Honoraria; certara: Honoraria; sanofi aventis: Honoraria; bms: Honoraria; syros: Honoraria; taiho: Honoraria; OncLive: Honoraria; actinium: Research Funding; aptose: Research Funding; boehringer ingelheim: Research Funding; h3bioscience: Research Funding; aprea: Research Funding; sellas: Research Funding; stemline: Research Funding. Litzow: Pluristem: Research Funding; Astellas: Research Funding; AbbVie: Research Funding; Jazz: Other: Advisory Board; Amgen: Research Funding; Actinium: Research Funding; Omeros: Other: Advisory Board; Biosight: Other: Data monitoring committee. Lin: AbbVie, Aptevo Therapeutics, Astellas Pharma, Bio-Path Holdings, Celgene, Celyad, Genentech-Roche, Gilead Sciences, Incyte, Jazz Pharmaceuticals, Novartis, Ono Pharmaceutical, Pfizer, Prescient Therapeutics, Seattle Genetics, Tolero, Trovagene: Research Funding. Foster: Agios: Consultancy; Daiichi Sankyo: Consultancy; Macrogenics: Consultancy; Rafael Pharmaceuticals: Research Funding; Macrogenics: Research Funding; Bellicum Pharmaceuticals: Research Funding. Cogle: Celgene: Membership on an entity's Board of Directors or advisory committees; Aptevo therapeutics: Research Funding. Vergilio: Roche: Current equity holder in publicly-traded company; Foundation Medicine: Current Employment. Gana: Bausch: Current holder of individual stocks in a privately-held company; The Leukemia & Lymphoma Society: Consultancy. Druker: The RUNX1 Research Program: Membership on an entity's Board of Directors or advisory committees; EnLiven: Consultancy, Research Funding; Amgen: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Aptose Therapeutics: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; GRAIL: Current equity holder in publicly-traded company; Nemucore Medical Innovations, Inc.: Consultancy; Merck & Co: Patents & Royalties; Novartis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Bristol-Myers Squibb: Research Funding; Cepheid: Consultancy, Membership on an entity's Board of Directors or advisory committees; Iterion Therapeutics: Membership on an entity's Board of Directors or advisory committees; Recludix Pharma, Inc.: Consultancy; Third Coast Therapeutics: Membership on an entity's Board of Directors or advisory committees; VB Therapeutics: Membership on an entity's Board of Directors or advisory committees; Aileron: Membership on an entity's Board of Directors or advisory committees; ALLCRON: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Vincerx Pharma: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Vivid Biosciences: Membership on an entity's Board of Directors or advisory committees. Byrd: Vincerx Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Novartis, Trillium, Astellas, AstraZeneca, Pharmacyclics, Syndax: Consultancy, Honoraria; Newave: Membership on an entity's Board of Directors or advisory committees. Levine: QIAGEN: Membership on an entity's Board of Directors or advisory committees; Imago: Membership on an entity's Board of Directors or advisory committees; Ajax: Membership on an entity's Board of Directors or advisory committees; Mission Bio: Membership on an entity's Board of Directors or advisory committees; Zentalis: Membership on an entity's Board of Directors or advisory committees; Lilly: Honoraria; Celgene: Research Funding; Isoplexis: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Research Funding; Incyte: Consultancy; Janssen: Consultancy; Astellas: Consultancy; Morphosys: Consultancy; Gilead: Honoraria; Amgen: Honoraria; C4 Therapeutics: Membership on an entity's Board of Directors or advisory committees; Prelude: Membership on an entity's Board of Directors or advisory committees; Auron: Membership on an entity's Board of Directors or advisory committees. Mims: Leukemia and Lymphoma Society: Consultancy; Kura Oncology: Consultancy; Genentech: Consultancy; Abbvie: Consultancy; Syndax Pharmaceuticals: Consultancy; BMS: Consultancy; Aptevo: Research Funding; Xencor: Research Funding; Glycomemetics: Research Funding; Jazz Pharmaceuticals: Consultancy; Daiichi-Saynko: Consultancy. OffLabel Disclosure: IVO is an oral potent inhibitor of mutated IDH1 enzyme, recently approved for the treatment of ND adult patients with IDH1m AML âââ,¬Â°Ã,Â¥75 years old or with comorbidities precluding use of intensive induction chemotherapy, and adult pts with relapsed or refractory AML. The combination of AZA, a hypomethylating agent, and venetoclax, an oral BCL-2 inhibitor, is also FDA approved for newly diagnosed AML in adults 75 years or older, or who have comorbidities precluding intensive chemotherapy. This presentation will discuss the combination of IVO and AZA.
Venetoclax and hypomethylating agents in older/unfit patients with blastic plasmacytoid dendritic cell neoplasm

American Journal of Hematology | November 22, 2021 | Volume: 97 | Issue: 2 | Pages: No page available

10.1002/ajh.26417 | PMID 34807470

Comparative study of therapy‐related and de novo adult b‐cell acute lymphoblastic leukaemia

British Journal of Haematology | October 26, 2021 | Volume: 196 | Issue: 4 | Pages: 963-968

10.1111/bjh.17906 | PMID 34697797

SummaryWe report a comparative analysis of patients with therapy‐related acute lymphoblastic leukaemia (tr‐ALL) vs de novo ALL. We identified 331 patients with B‐ALL; 69 (21%) were classified as tr‐ALL. The most common prior malignancies were breast (23·2%) and plasma cell disorders (20·3%). Patients with tr‐ALL were older (median 63·2 vs. 46·2 years, P < 0.001), more often female (66·7% vs. 43·5%, P < 0·001), and more likely to have hypodiploid cytogenetics (18·8% vs. 5·0%, P < 0·001). In multivariable analysis, patients with tr‐ALL were less likely to achieve complete remission [odds ratio (OR) = 0·16, P < 0·001] and more likely to be minimal residual disease‐positive (OR = 4·86, P = 0·01) but had similar OS after diagnosis and allo‐haematopoietic cell transplantation.
Genetic features and clinical outcomes of patients with isolated and comutated DDX41 -mutated myeloid neoplasms

Blood Advances | October 18, 2021 | Volume: 6 | Issue: 2 | Pages: 528-532

10.1182/bloodadvances.2021005738 | PMID 34644397

Abstract DDX41 mutations (germline and somatic) are associated with late onset myelodysplastic syndromes/acute myeloid leukemia (MDS/AML). Myeloid neoplasms (MN) with germline predisposition was identified as a distinct category in the 2016 WHO classification revision, including MN with germline DDX41 mutation. We retrospectively analyzed the molecular findings and clinical characteristics of thirty-three DDX41-mutated (mDDX41) patients at our institution. We identified 14 distinct pathogenic DDX41 variants in 32 patients and 8 DDX41 variants of unknown significance (VUS) in 9 patients. Five (16%) patients had a second DDX41 somatic mutation p.R525H and 13 (40%) had at least one additional oncogenic co-mutation in other genes. The median age at the time of diagnosis was 66 years, with male predominance (72%) and the majority of patients had normal cytogenetics (91%). Two-year overall survival (OS) was 86% and 6 (21%) MDS/AML patients with relatively preserved hematopoietic function were observed without further intervention. In comparison to AML patients with prognostically more favorable subtypes [t(8;21), n=27 and inv(16), n=40], mDDX41 patients in our cohort showed similarly favorable OS. Our study highlights that mDDX41-MN patients often have an indolent course and mDDX41-AML has comparable OS to favorable-risk AML.
Outcomes of venetoclax‐based therapy in chronic phase and blast transformed chronic myelomonocytic leukemia

American Journal of Hematology | August 24, 2021 | Volume: 96 | Issue: 11 | Pages: No page available

10.1002/ajh.26334 | PMID 34428328

Blood and Marrow Transplant Clinical Trials Network Study 1102 heralds a new era in hematopoietic cell transplantation in high‐risk myelodysplastic syndromes: Challenges and opportunities in implementation

Cancer | August 10, 2021 | Volume: 127 | Issue: 23 | Pages: 4339-4347

10.1002/cncr.33826 | PMID 34375439

Lay Summary People who have advanced myelodysplastic syndromes (MDS) may live longer if they get a bone marrow transplant (BMT) instead of other therapies. However, only 15% of people with MDS actually get BMT. Experts say community physicians and transplant physicians should team up with insurance companies and patient advocacy groups to 1) spread this news about lifesaving advances in BMT, 2) ensure that everyone can afford health care, 3) provide emotional support for patients and families, 4) help patients and families get transportation and housing if they need to travel for transplant, and 5) improve care for people of under‐represented racial and ethnic backgrounds.
Reduced intensity conditioning for acute myeloid leukemia using melphalan- vs busulfan-based regimens: a CIBMTR report

Blood Advances | July 1, 2021 | Volume: 4 | Issue: 13 | Pages: 3180-3190

10.1182/bloodadvances.2019001266 | PMID 32663298

Abstract There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P &lt; .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P &lt; .001). Long-term relapse was lower with FM (HR = 0.65, P &lt; .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.
Open-Label Phase II Prospective, Randomized, Controlled Study of Romyelocel-L Myeloid Progenitor Cells to Reduce Infection During Induction Chemotherapy for Acute Myeloid Leukemia

Journal of Clinical Oncology | June 22, 2021 | Volume: 39 | Issue: 29 | Pages: 3261-3272

10.1200/jco.20.01739 | PMID 34156898

PURPOSEStandard cytotoxic induction chemotherapy for acute myeloid leukemia (AML) results in prolonged neutropenia and risk of infection. Romyelocel-L is a universal, allogeneic myeloid progenitor cell product being studied to reduce infection during induction chemotherapy.PATIENTS AND METHODSOne hundred sixty-three patients with de novo AML (age ≥ 55 years) receiving induction chemotherapy were randomly assigned on day 0 (d0), of whom 120 were evaluable. Subjects received either romyelocel-L infusion on d9 with granulocyte colony-stimulating factor (G-CSF) starting daily d14 (treatment group) or G-CSF daily alone on d14 (control) until absolute neutrophil count recovery to 500/µL. End points included days in febrile episode, microbiologically defined infections, clinically diagnosed infection, and days in hospital.RESULTSMean days in febrile episode was shorter in the treatment arm from d15 through d28 (2.36 v 3.90; P = .02). Similarly, a trend toward decreased microbiologically defined infections and clinically diagnosed infection in the treatment arm was observed from d9 to d28 (35.6% v 47.5%; P = .09), reaching a statistically significant difference from d15 to d28 (6.8% v 27.9%; P = .002). Because of this, antibacterial or antifungal use for treatment of an infection was significantly less in the treatment group (d9-d28: 44.1% v 63.9%; P = .01). Significantly fewer patients in the treatment arm received empiric antifungals from d9 tod28 (42.4% v 63.9%; P = .02) and d15-d28 (42.4% v 62.3%; P = .02). Patients in the treatment arm also had 3.2 fewer hospital days compared with control (25.5 v 28.7; P = .001). Remission rates and days to absolute neutrophil count recovery were similar in the two groups. No patients in the romyelocel-L plus G-CSF group died because of infection compared with two patients in the control arm. No graft-versus-host disease was observed.CONCLUSIONSubjects receiving romyelocel-L showed a decreased incidence of infections, antimicrobial use, and hospitalization, suggesting that romyelocel-L may provide a new option to reduce infections in patients with AML undergoing induction therapy.
Patient perceptions of palliative care in the process of allogeneic hematopoietic cell transplantation.

Journal of Clinical Oncology | June 2, 2021 | Volume: 39 | Issue: 15_suppl | Pages: e24082-e24082

10.1200/jco.2021.39.15_suppl.e24082

e24082 Background: Allogeneic hematopoietic cell transplantation (allo-HCT) is associated with significant short- and long-term sequelae that affect patients’ overall quality of life (QoL) and their physical and psychological well-being. Studies have shown improvement in patient QoL and physician satisfaction with palliative care involvement in the allo-HCT process. However, patient and physician perceptions regarding palliative care often impact timely referral. We conducted a prospective study to examine patient perceptions of palliative care both before and after palliative care consultation during evaluation for allo-HCT. Methods: This is a prospective, single-center study, of patients > 18 years of age, who were referred for a palliative care consultation as part of standard evaluation for allo-HCT. Patients were administered a pre- and post-visit internally derived questionnaire to assess their understanding and comfort level with palliative care. The primary objective of this study was to examine patient perceptions of palliative care consultation during evaluation for allo-HCT. Primary end point was the change in patient pre- and post- questionnaire responses. Secondary endpoint was the completion of advance care planning documentation pre- and post- consultation. Results: We enrolled 32 patients (male = 14) undergoing evaluation for allo-HCT with a primary diagnosis of AML (n = 8), NHL (n = 8), MDS (n = 7), ALL (n = 2), and other (n = 7). Following consultation with palliative care there was a statistically significant increase in patient understanding of the reason for the appointment, p = 0.0006. There was also a significant increase in patient’s knowledge of palliative care, with only 28% describing their knowledge as “good” or “excellent” prior to consultation and 79.3% after consultation, p < 0.0001. There was an observed positive, non-statistically significant, trend in patient comfort level with palliative medicine with only 20.7% (n = 6) describing their comfort as “high” or “very high” prior to consultation and 51.7% (n = 15) after consultation, p = 0.60. There was a higher rate of completion of advance care planning documentation following consultation with palliative medicine 56.3% vs 71.4%, p = 0.042. Conclusions: Palliative care consultation prior to allo-HCT increases a patient’s understanding of the role of palliative medicine as part of their allo-HCT and improves advance care planning. These findings need to be validated in a larger, multicenter, patient cohort.
Adult Philadelphia-like B-cell acute lymphoblastic leukemia: Characteristics, outcomes, and role of allogeneic hematopoietic cell transplantation in comparison to Philadelphia-positive and Philadelphia-negative acute lymphoblastic leukemia.

Journal of Clinical Oncology | June 2, 2021 | Volume: 39 | Issue: 15_suppl | Pages: 7022-7022

10.1200/jco.2021.39.15_suppl.7022

7022 Background: Philadelphia-like Acute Lymphoblastic Leukemia (Ph-like ALL) is a high-risk subset of adult ALL. Until recently, there has not been a systematic platform to recognize this entity in clinical practice. Furthermore, data regarding the role of allogeneic hematopoietic cell transplantation (allo-HCT) is lacking. We conducted this study to identify patients with Ph-like ALL and describe their outcomes in comparison to Ph+ and Ph- ALL with emphasis on the role of allo-HCT. Methods: To identify cases of Ph-like ALL, available diagnostic cytogenetic pellets for patients in the Mayo Clinic ALL cohort (N=365) were tested using a targeted fluorescence in situ hybridization (FISH) panel developed by the Mayo Clinic Genomics Laboratory and includes probes to detect Ph-like-specific rearrangements (i.e., ABL1, ABL2, PDGFRB, JAK2 and CRLF2). Results: Thirty-three (9%) patients with Ph-like ALL were identified, the remaining patients were classified as Ph+ (N=132, 36%) or Ph- ALL (N=200, 55%). Patients with Ph-like ALL were younger (Median: 39 vs. 50 vs. 49 years, P=.01), had higher WBC (Median: 27.9 vs. 21.5 vs. 4.5 x109/L, P<.001), were less likely to achieve CR (91% vs. 99% vs. 96%, P=.02), more likely to be MRD+ (64% vs. 34% vs. 36%, P=.03), had a higher relapse rate (5-year: 39% vs. 24% vs. 38%, P=.01) and lower OS (5-year: 41% vs. 64% vs. 49%, P=.02), see Table. Patients who achieved MRD negativity had better OS (MRD+ vs MRD-, P=.01). Importantly, no statistically significant difference in OS, relapse or non-relapse mortality were noted between the 3 groups in patients who underwent allo-HCT in CR1. Conclusions: Ph-like ALL is a high risk subgroup with increased prevalence in younger adults. Allo-HCT appears to offset the poor prognosis associated with this entity. A targeted FISH panel offers timely recognition of this entity in a clinical setting.[Table: see text]