Belangrijke abstracten van ASCO 2018 op het gebied van vormen van hematologische vormen van kanker zoals lymfklierkanker, CLL, Waldenstrom copy 1 copy 1 copy 1

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30 mei 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 multiple myeloma (Kahler) , CLL - Chronische lymfastische leukemie, lymfklierkanker, ziekte van Waldenström..

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 dr. David Strauss die we hierbij overnemen van ASCO Post

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

7500 RELEVANCE: Phase III randomized study of lenalidomide plus rituximab (R2) versus chemotherapy plus rituximab, followed by rituximab maintenance, in patients with previously untreated follicular lymphoma. NH Fowler, F Morschhauser, P Feugier, et al

Tale-Home Message

In this phase III trial, 1030 patients with follicular lymphoma and high tumor burden were randomized to receive lenalidomide plus rituximab (R2; 513 patients) or chemotherapy plus rituximab (R-chemo; 517 patients), both followed by rituximab maintenance. Complete response/unconfirmed complete response and progression-free survival at 120 weeks were not significantly different between groups. More frequent grade 3/4 lab and febrile neutropenia events were reported in patients receiving R-chemo, whereas more frequent grade 3/4 cutaneous events were reported in patients receiving R2. Approximately 70% of patients in each arm completed treatment.
These results demonstrate that R2 has similar efficacy and different toxicities compared with R-chemo in patients with follicular lymphoma.

7501 Acalabrutinib in patients (pts) with Waldenström macroglobulinemia (WM). R Owen, H McCarthy, S Rule, et al

Take-Home Message

In this study, 106 patients with treatment-naïve or relapsed/refractory Waldenström’s macroglobulinemia (WM) were given 100 mg acalabrutinib in 28-day cycles until progressive disease or intolerance. After 25 months of follow-up, 50% of treatment-naïve patients and 76% of relapsed/refractory patients remain on treatment. Commonly reported adverse events include neutropenia, pneumonia, anemia, increased ALT, and hyponatremia. Grade 5 adverse events were pneumonia, glioblastoma multiforme, esophageal carcinoma, myocardial ischemia, and intracranial hematoma. The overall response rate was 93% and 94% and the duration of response was 90% and 84% in patients with treatment-naïve and relapsed/refractory disease, respectively.
These results demonstrate the tolerability of acalabrutinib and the striking efficacy in patients with WM.

7503 Randomized phase III study comparing an early PET driven treatment de-escalation to a not PET-monitored strategy in patients with advanced stages Hodgkin lymphoma: Final analysis of the AHL2011 LYSA study. O Casasnovas, P Brice, R Bouabdallah, et al

Take-Home Message

In this study, 823 patients with stage III, IV, or high-risk IIB Hodgkin’s lymphoma were treated with two cycles of BEACOPP and then underwent PET. A treatment approach driven by results of PET called for four cycles of ABVD for PET-negative patients and four cycles of BEACOPP for PET-positive patients (arm B) compared with the standard treatment approach of a total of six cycles of BEACOPP (arm A). The PET positivity rate was similar in both arms. Based on PET results, 84% of patients in arm B received four cycles of ABVD and 12% of patients in arm A received four additional cycles of BEACOPP. Significantly more frequent grade 3 or higher adverse events were reported in arm A. The 5-year progression-free survival rate was similar in both arms. Patients who had positive PET results had significantly shorter 5-year progression-free survival compared with patients who had negative PET results.
PET after two cycles of BEACOPP can guide subsequent treatment, supporting the use of ABVD for patients with negative PET results.

7504 Activity and tolerabilty of the first-in-class anti-CD47 antibody Hu5F9-G4 with rituximab tolerated in relapsed/refractory non-Hodgkin lymphoma: Initial phase 1b/2 results. RH Advani, I Flinn, L Popplewell, et al

Take-Home Message

In this phase IB/II study, 22 heavily pretreated patients with relapsed/refractory DLBCL and follicular lymphoma were given a 1 mg/kg 5F9 priming dose with maintenance doses escalating from 10 to 30 mg/kg plus standard rituximab. Commonly reported treatment-related adverse events were chills, headache, anemia, and fever. The maximum tolerated dose was not reached, and the recommended phase II dose was 30 mg/kg 5F9 every 2 weeks after cycle 1. The overall response rate was 50%, with 32% achieving complete responses. At data cutoff, 90% of responding patients maintained their response at a median 4.4 months of follow-up.
These results demonstrate the promising activity and tolerability of 5F9 plus rituximab in patients with follicular lymphoma and DLBCL.

7505 Updated safety and long term clinical outcomes in TRANSCEND NHL 001, pivotal trial of lisocabtagene maraleucel (JCAR017) in R/R aggressive NHL. JS Abramson, LI Gordon, ML Palomba, et al

Take-Home Message

This study was designed to assess overall safety (n = 91) and efficacy (n = 88) of lisocabtagene maraleucel (liso-cel) in patients with relapsed/refractory DLBCL. Cytokine release syndrome and neurotoxicity developed in 35% and 19% of patients, respectively, including grade 3/4 events in 1% and 12%, respectively. The best overall response rate in the FULL and CORE datasets were 74% and 80%, with a best complete response of 52% in FULL and 55% in CORE. At dose level two, an increased rate of durable response was reported in the CORE dataset compared with dose level one.
Long-term safety and efficacy data will be reported.

7507 Randomized phase 2 trial of polatuzumab vedotin (pola) with bendamustine and rituximab (BR) in relapsed/refractory (r/r) FL and DLBCL. LH Sehn, M Kamdar, A Francisco, et al

Take-Home Message

In this study, 160 transplant-ineligible patients with follicular lymphoma or DLBCL were randomized to receive polatuzumab vedotin (pola) plus bendamustine and rituximab (BR) or BR for six cycles. Patients receiving pola plus BR more frequently suffered cytopenia, febrile neutropenia, and infections compared with patients receiving BR. Similar rates of grade 5 adverse events were reported in both treatment arms. Patients with DLBCL who received pola plus BR exhibited significantly higher PET complete response rates and significantly longer median progression-free and overall survival in second line, third line and beyond.
These results demonstrate the tolerability of pola + BR in this patient population. Patients with DLBCL who received pola plus BR exhibited improved survival regardless of prior therapy. Further follow-up is needed to evaluate survival in patients with follicular lymphoma.

Session: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
Monday June 4, 8:00 AM–11:30 AM

7511 The dual SYK/JAK inhibitor cerdulatinib demonstrates rapid tumor responses in a phase 2 study in patients with relapsed/refractory B- and T-cell non-Hodgkin lymphoma (NHL). PA Hamlin, BD Cheson, CM Farber, et al

Take-Home Message

In this phase IIA study, 99 patients in patients with relapsed/refractory B- and T-cell non-Hodgkin’s lymphoma were given cerdulatinib 30 mg orally twice daily, with dose reductions permitted to a minimum of 15 mg twice daily. Grade 3 or higher adverse events occurring in at least 5% of patients included neutropenia, lipase increase, pneumonia, diarrhea, and fatigue. The overall response rate was 61% in patients with CLL/SLL, 50% in patients with follicular lymphoma, and 43% in those with peripheral T-cell lymphoma (4 complete responses and 2 partial responses in 14 patients). Patients who relapsed on venetoclax, tenalisib, and BTK inhibitor therapy achieved durable partial responses.
These results demonstrate the safety and promising efficacy of cerdulatinib 30 mg twice daily in patients with relapsed/refractory B- and T-cell non-Hodgkin’s lymphoma.

7512 Durability of response to venetoclax (VEN) in patients with CLL relapsed/refractory to ibrutinib and/or idelalisib. JC Byrd, WG Wierda, MS Davids, et al

Take-Home Message

In this study, 122 patients with CLL relapsed/refractory to idelalisib and/or ibrutinib were given venetoclax 400 mg daily and outcomes were evaluated. The best overall response rate was 66% after a median of 17 months of treatment with venetoclax. Per investigator review, the median progression-free survival was 25 months and the duration of response and median overall survival were not reached. Undetectable blood minimal residual disease (MRD) was reported in 36 of 77 patients assessed, with 9 of 26 patients having undetectable marrow MRD. Patients with undetectable MRD in the blood had significantly prolonged progression-free survival compared with patients who had positive MRD. The most frequently reported adverse events were diarrhea, nausea, and cytopenias.
Venetoclax has acceptable tolerability, high activity, and durability in patients with CLL relapsed/refractory to idelalisib and/or ibrutinib.

Session: Hematologic Malignancies—Plasma Cell Dyscrasia
Friday June 1, 2:45 PM–5:45 PM

8004 Phase 2 study of venetoclax plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma. LJ Costa, EAllen Stadtmauer, GJ Morgan, et al

Take-Home Message

In this phase II dose-escalation study, 26 patients with relapsed/refractory multiple myeloma (R/R MM) received venetoclax combined with carfilzomib and dexamethasone (VENKd) on 28-day cycles. At data cutoff, 3 patients discontinued due to death, physician decision, and progressive disease. Adverse events were reported in 85% of patients, with grade 3/4 events of neutropenia, hypertension, thrombocytopenia, decreased white blood cells, and nausea. No dose-limiting toxicities were reported, and the maximum tolerated dose was not reached. Of 17 evaluable patients who completed at least two cycles, 3 achieved a complete response, 2 achieved a very good partial response, 3 achieved a partial response, 3 achieved stable disease, and 2 experienced progressive disease. Of 5 evaluable patients with t(11;14) MM, 1 achieved a complete response, 1 achieved a very good partial response, and 3 had progressive disease.
These results demonstrate that VENKd is well-tolerated and has promising efficacy. A phase III trial is planned.

8008 FDA analysis of pembrolizumab trials in multiple myeloma: Immune related adverse events (irAEs) and response. AC Krauss, F Mulkey, Y-L Shen, et al

Take-Home Message

This study assessed overall survival, objective response rates (ORR), and safety based on development of immune-related adverse events (irAE) among 249 patients randomized in KEYNOTE-183 and 301 patients randomized in KEYNOTE-185. In KEYNOTE-183, the overall survival hazard ratio was 1.61, with 29 deaths in the pembrolizumab arm and 21 in the control arm. The ORR was 34% and 40% in the pembrolizumab arm and the control arm, respectively. A total of 58% of patients receiving pembrolizumab developed an irAE, with no difference reported in ORR between patients who did or did not develop an irAE (37% vs 31%). In KEYNOTE-185, the overall survival hazard ratio was 2.06, with 19 deaths in the pembrolizumab arm and 9 in the control arm. The ORR was 64% and 62% in the pembrolizumab arm and the control arm, respectively. The ORR was higher in patients who developed an irAE compared with those who did not.
These results highlight the significant incidence of irAEs, warranting further study of immunotherapy in patients who are unable to mount adequate immune responses.

CLL - chroniche lymfatische Leukemie, lymfklierkanker, non-Hodgkin, hematologische vormen van kanker, ASCO 2018, abstracten, Kahler, multiple myeloma