PracticeUpdate: Haematology & Oncology

CONFERENCE COVERAGE 16

Dr Isabel Cunningham discusses her top abstracts fromASH 2016

Isabel Cunningham, MD, is Adjunct Associate Research Scientist, Division of Hematology Oncology, Columbia University College of Physicians and Surgeons in New York, and Associate Editor of PracticeUpdate Oncology .

months following treatment, which preceded clinical relapse by a median of 25 months. This study demonstrates that IGHV-M is the best pretreatment predictor of achieving MRD negativity and longer PFS; however, many patients relapse, which can be moni- tored in peripheral blood to direct interven- tion strategies. Clinical allogeneic transplantation: results Abstract 521: Combining flow cytometry and molecular assessment improves the prognostic value of pre-transplant minimal residual disease in acute myeloid leukemia. F Guolo, P Minetto, F Galaverna, et al This retrospective study evaluated out- comes of 224 consecutive AML patients who received allo-BMT in first or second CR. Relapse occurred in 27.7% of patients. Combined MRD analysis and onset of acute GVHD were significant predictors of cumu- lative incidence of relapse. MRD evaluation predicted long-term survival, with significant influences of conditioning intensity and com- bined MRD evaluation on OS duration. These results demonstrate that pretransplant MRD evaluation via molecular and multi- colour flow cytometry assessment reliably predicts risk of relapse, which may be used to tailor therapeutic strategies for patients. Acute myeloid leukaemia: clinical studies Abstract 591: Vadastuximab talirine plus hypomethylating agents: a well-tolerated regimen with high remission rate in frontline older patients with acute myeloid leukemia (AML). AT Fathi, HP Erba, JE Lancet, et al This phase 1 study included 53 patients with previously untreated CD33-positive AML who received vadastuximab talirine (33A) plus hypomethylating agents to evaluate the safety, tolerability, pharmacokinetics, and antileukemic activity. The median treatment duration currently is 19.3 weeks, with 13 patients continuing treatment. No dose- limiting toxicities, infusion reactions, or grade 4/5 bleeding were reported. Grade 3/4 adverse events included thrombocytopenia, anaemia, febrile neutropenia, pneumonia, and leukopenia. Non-haematological AEs included fatigue, nausea, constipation, pyrexia, dyspnoea, and diarrhoea. No treatment-related deaths were reported. Of the 49 evaluable patients, 73% achieved CR or CRi. Of the 22 evaluable patients

Acute myeloid leukaemia: novel therapy, excluding transplantation Abstract 102: Safety and efficacy of venetoclax plus low-dose cytarabine in treatment-naive patients aged ≥65 years with acute myeloid leukemia. A Wei, SA Strickland, GJ Roboz, et al This study enrolled 20 patients with treatment- naive AML (expansion, n=12; escalation, n=8) with a median age of 74 years who were ineligible for anthracycline-containing induction chemotherapy. The median time on venetoclax was 147.5 days. The most commonly reported grade 3/4 AEs included febrile neutropenia (35%), hypophosphatemia (20%), and hypertension (20%). Venetoclax exposures both with and without low-dose cytarabine were comparable. Of the 15 of patients who achieved an objective response, 14 had a CR+CRi, all of whom had no prior myeloproliferative neoplasm. For all patients, the 12-month OS was 74.7%; for responders, 12-month OS was 86.7%. These findings demonstrate the safety of venetoclax plus low-dose cytarabine in older patients with treatment-naive AML and sug- gest that the improved survival in responders is due to treatment with venetoclax plus low- dose cytarabine. Acute lymphoblastic leukaemia: therapy, excluding transplantation Abstract 176: Final results of Northern Italy Leukemia Group (NILG) Trial 10/07 combining pediatric-type therapy with minimal residual disease study and risk-oriented hematopoietic cell transplantation in adult acute lymphoblastic leukemia (ALL). R Bassan, A Masciulli, T Intermesoli, et al This study included 205 patients withALL (42 Ph+ ALL, 119 Ph− B-ALL, and 44 T-ALL) with a median age of 41 years who received combined paediatric-type therapy (PTT) with minimal residual disease (MRD) study for risk- oriented HCT. The CR rate was 98% in T-ALL and Ph+ ALL, whereas the CR rate was 83% in Ph− B-ALL, with a significantly higher rate in patients ≤ 60 years. In 109/142 CR patients with Ph−ALL, theMRD study was successful and contributed to risk classification in 41 MRD-responsive and 22 MRD-resistant

patients. Overall, the maintenance allocation group consisted of 55 CR patients, and the HCT allocation group included 87 patients, with 43% selected for HCT independently of MRD results. Intention-to-treat analyses revealed overall survival of 53% at 5 years, with the median not reached; the median DFS is 4.8 years. Patients with Ph− ALL had 5-year OS/DFS rates of 74%/61% in T-ALL (medians not reached) and 48%/48% in B-ALL (medians, 3.9 and 4.7 years). DFS was significantly improved in patients with an MRD response <10 −4 compared with patients with MRD ≥ 10 −4 . These findings support the applicability of the combined PTT/MRD-based risk-oriented strategy in adults with ALL, with some decreased effects in patients >60 years. CLL: therapy, excluding transplantation Abstract 232: Early achievement of MRD- negativity in IGHV-mutated (IGHV-M) patients portends highly favorable outcomes after first-line treatment of CLL with fludarabine, cyclophosphamide and rituximab (FCR). Serial monitoring for minimal residual disease (MRD) in blood after achieving MRD-negativity predicts subsequent clinical relapse. PA Thompson, P Strati, M Keating, et al This prospective study included 289 patients with CLL who received first-line FCR between 2008 and 2015 to evaluate the time course and predictive factors for relapse in initially MRD-negative patients. A total of 95 MRD-negative patients underwent 12-month serial MRD blood monitoring. In the total cohort, only IGHV-unmutated (IGHV-UM) was significantly associated with PFS. Upon separate analysis, IGHV-mutated (IGHV-M) patients demonstrated a significant association between ZAP70 positivity and shorter PFS, whereas IGHV-UM patients demonstrated a significant association between B2M ≥ 4.0 mg/L and shorter PFS. The overall response rate was 96%, with 51% of patients at EOT achieving MRD negativity in bone marrow, which was significantly associated IGHV-M in multivariable analysis. In blood, re- emergence of MRD was detected in 45/95 MRD-negative patients after a median of 49

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