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30 mei 2018: ASCO 2018

ASCO 2018

A.s. weekend start ASCO 2018 in Chicago. Hier een selectie van belangrijke abstracten binnen het gebied van hematologische vormen van kanker zoals vormen van leukemie ook wel worden genoemd.

Klik op de nummers voor de abstracten zelf. We zullen komende week zeker een aantal abstracten eruit kiezen om die wat uitgebreider te beschrijven maar hier alvast een voorselectie door hematologe Isabel Cunningham die we hierbij overnemen van ASCO Post

Session: Health Services Research, Clinical Informatics, and Quality of Care
Saturday June 2, 1:15 PM–4:45 PM 

6594 CYP2C19-guided voriconazole prophylaxis in neutropenic AML patients. JK Hicks, K Shahbazian, RE Quilitz, et al  

Take-Home Message

  • In this study, 193 patients with AML underwent CYP2C19 genotyping in an attempt to optimize prophylactic voriconazole dosing. Voriconazole was given to 154 patients for prophylaxis and 11 for treatment; it was not given to 28 patients. Of the patients receiving voriconazole, 89% were dosed per CYP2C19-guided recommendations. CYP2C19-guided dosing led to target trough concentrations in 70.1% of patients.
  • These results demonstrate the feasibility of using CYP2C19 genotyping to guide voriconazole dosing, with 70% of patients achieving goal trough concentrations.

Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
Saturday June 2, 3:00 PM–6:00 PM 

7000 Ivosidenib (IVO; AG-120) in mutant IDH1 relapsed/refractory acute myeloid leukemia (R/R AML): Results of a phase 1 study. DA Pollyea, CD Dinardo, S de Botton, et al 

Take-Home Message 

  • In this study, 258 patients with relapsed/refractory AML received ivosidenib. At data cutoff, 17 of 179 patients who received ivosidenib 500 mg once daily remained on treatment. The rate of complete remission with partial hematologic recovery was 31.8%, including complete remission in 24% of patients. The median duration of complete remission with partial hematologic recovery was 8.2 months. The overall response rate was 41.9%. The most frequently reported adverse events were grades 1/2 and unrelated to treatment. IDH differentiation syndrome was reported in 10.6% of patients, with the study drug associated in 3.4%, but it did not result in dose reduction, treatment discontinuation, or death.
  • Ivosidenib was well-tolerated and induced durable remission in patients with relapsed/refractory AML. 

7001 Association of early intervention in transfusion independent (TI) patients (Pts) with lower-risk myelodysplastic syndromes (MDS) treated with attenuated doses of hypomethylating agents (HMAs) with high response rates and long duration of response. M Swaminathan, E Jabbour, F Ravandi, et al 

Take-Home Message

  • In this study, the response of 87 patients with transfusion independent low-risk (n = 30) or intermediate-1 risk (n = 57) MDS who were treated with hypomethylating agents from 2012 to 2017 was assessed. Of the 80 evaluable patients, the overall response rate was 74%, including 40 complete responses. Median event-free survival was 35.4 months, and median overall survival was not reached. Progressive disease was reported in 2 patients, 19 had no response, and 6 progressed to acute myeloid leukemia.
  • Early hypomethylating agent intervention in transfusion-independent patients who have lower-risk MDS was found to be safe and effective.

7003 Long-term treatment-free remission (TFR) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) after stopping second-line (2L) nilotinib: ENESTop 144-wk results. F-X Mahon, C Boquimpani, N Takahashi, et al 

Take-Home Message

  • This study was designed to assess treatment-free remission (TFR) in 126 patients with chronic-phase CML who entered TFR in the ENESTop study. Of these patients, 61 remained in TFR, 58 restarted nilotinib, and 7 discontinued the study. At week 144, the TFR rate was 48.4%. Of 34 patients who restarted nilotinib due to loss of MMR, 97.1% regained MMR and 91.2% regained MR5. The 144-week treatment-free survival rate was 52%.
  • These results highlight the long-term durability of TFR following nilotinib treatment and emphasize the importance of routine monitoring for late loss of response.

7004 Moxetumomab pasudotox in heavily pretreated patients with relapsed/refractory hairy cell leukemia: Results of a pivotal international study. RJ Kreitman, C Dearden, PL Zinzani, et al 

Take-Home Message

  • This single-arm, multicenter study was designed to determine the effects of moxetumomab pasudotox in 83 patients with relapsed/refractory hairy cell leukemia who received a median of three prior therapies. The objective response rate was 75% at a median of 16.7 months of follow-up. The rate of hematologic remission was 80%, the complete response rate was 41%, and the durable complete response rate was 30%. Of the 33 patients who achieved complete remission, 27 had IHC MRD-negative status. The most frequently reported treatment-related adverse events were nausea, peripheral edema, headache, and pyrexia. Treatment-related adverse events leading to discontinuation include hemolytic uremic syndrome, capillary leak syndrome, and increased blood creatinine.
  • These results demonstrate the potential of moxetumomab pasudotox to induce durable complete responses without immuno/myelosuppression in heavily pretreated patients with hairy cell leukemia. 

7006 Outcomes of patients (pts) treated with prior blinatumomab (Blin) in ZUMA-3: A study of KTE-C19, an anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in adult pts with relapsed/refractory acute lymphoblastic leukemia (R/R ALL). BD Shah, OO Oluwole, MR Baer, et al 

Take-Home Message 

  • In this study, 29 patients with relapsed/refractory ALL treated with KTE-C19 were evaluable for safety, with 24 of them were evaluable for efficacy. Patients who previously received blinatumomab (n = 11) had worse performance status and were more likely to be relapsed/refractory to second-line or greater therapy. After 8 weeks of follow-up, 63% of patients who previously received blinatumomab and 75% of patients who did not previously receive blinatumomab achieved complete responses or complete responses with incomplete hematologic recovery. Minimal residual disease–negative remission was reported in 88% of patients. Similar proportions of naïve and effector memory T cells were reported in patients with and without prior blinatumomab treatment.
  • These results demonstrate the promising efficacy and manageable safety profile of KTE-C19 in patients with relapsed/refractory ALL. 

Session: Pediatric Oncology II
Sunday June 3, 8:00 AM–11:00 AM 

10509 Subsequent malignant neoplasms (SMNs) among non-irradiated survivors of childhood cancer treated with chemotherapy in the Childhood Cancer Survivor Study. LM Turcotte, Q Liu, Y Yasui, et al 

Take-Home Message

  • Subsequent malignant neoplasms (SMNs) were reported among 139 5-year survivors of childhood cancer who were diagnosed between 1970 and 1999 and treated with chemotherapy. Among this group, there were 154 SMNs. The cumulative incidence at 30 years was 4.5%. Risk of SMNs was greater for survivors of leukemia, lymphoma, and sarcoma.
  • These results demonstrate that survivors of childhood cancer who are not exposed to radiation therapy have a higher risk of developing SMNs and should be counseled accordingly.

Session: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
Sunday June 3, 9:45 AM–12:45 PM 

7508 High, durable minimal residual disease negativity (MRD–) with venetoclax + rituximab (VenR) in relapsed/refractory (R/R) CLL: MRD kinetics from phase 3 MURANO study. P Hillmen, AP Kater, JF Seymour, et al 

Take-Home Message

  • In this study, patients with relapsed/refractory CLL were randomized to venetoclax plus rituximab (VenR) for 6 months, followed by venetoclax or bendamustine plus rituximab, and minimal residual disease (MRD) was assessed. A higher concordance between peripheral blood and bone marrow MRD negativity was reported. The best MRD-negative rates were higher in patients who received VenR, and were independent of high-risk factors only for VenR, including del(17p), IGVH unmutated, and mutated TP53 status. At the end of combination treatment, 121 of 194 patients on VenR were MRD negative, and, of these, 83% maintained MRD negativity at a median follow-up of 13.8 months.
  • VenR treatment led to durable MRD negativity in peripheral blood regardless of risk features.

Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
Monday June 4, 8:00 AM–11:30 AM 

7033 Hypomethylating agent (HMA) treatment as a bridge to allogeneic hematopoietic cell transplantation (HCT) for relapsed/refractory acute myeloid leukemia (RR-AML). MR Grunwald, D Boselli, LM Bohannon, et al 

Take-Home Message

  • In this study, 50 patients with relapsed/refractory AML who received hypomethylating agents (HMA) as a bridge to transplant between August 2013 and August 2017 were assessed to determine response and survival outcomes. At diagnosis, NCCN risk categories were 14% favorable, 32% intermediate, and 54% unfavorable. Lenalidomide was given concomitantly with HMA in 28% of patients, and 16% received sorafenib. The overall response rate was 57% among 37 evaluable patients; the overall response rate for the entire cohort was 42%. Significantly longer overall survival was reported in patients naïve to HMAs compared with patients who had had previous HMA exposure (13.0 vs 5.3 months). In 14 patients who underwent cell transplant following HMA therapy, 1-year overall survival was 100%, and 2-year overall survival was 78%.
  • HMA therapy led to comparable response and survival rates to other, more toxic, treatment in patients with relapsed/refractory AML, warranting further validation in a prospective study.

7528 Change in tumor lysis syndrome risk after lead-in treatment in a phase 1b/2 study of obinutuzumab, ibrutinib, and venetoclax for chronic lymphocytic leukemia. KA Rogers, Y Huang, AS Ruppert, et al 

Take-Home Message

  • This study assessed 61 patients with CLL (36 relapsed/refractory, 25 treatment-naïve) who completed three cycles of treatment with obinutuzumab, ibrutinib, and venetoclax. Absolute lymphocyte count and lymph node diameters decreased significantly. Ibrutinib lymphocytosis was attenuated by obinutuzumab treatment. Tumor lysis syndrome risk decreased from high to medium in 12 patients, from medium to low in 26 patients, and 23 had no change. No clinical or laboratory tumor lysis syndrome was reported.
  • These results showed that using lead-in obinutuzumab and ibrutinib decreased the risk of tumor lysis syndrome in many patients at medium or high risk for tumor lysis syndrome, which may improve the safety of initiating venetoclax.

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