HEMATOLOGY

Following the 2019 ASH Annual Meeting, Targeted Oncology spoke with experts from various specialties in hematology. The experts highlighted some of the top abstracts from the meeting that will impact the way multiple myeloma, leukemias, MPNs, and lymphomas are treated.

In an interview with Targeted Oncology, Jorge J. Castillo, MD, discussed the findings from the prospective phase II trial evaluating venetoclax in patients with Waldenström macroglobulinemia. He also addressed the unmet needs in this patient population and the next steps for research in the field.

In the phase III BELIEVE trial, clinically meaningful and durable transfusion burden reduction were observed with luspatercept in the majority of adult patients with β-thalassemia who require regular red blood cell. Additionally, dose levels were not associated with by incidence of adverse events, and these AEs decreases overtime without affecting treatment modification or continuation.

Treatment with REGN1979, a human anti-CD20 &times; anti-CD3 bispecific IgG4 antibody, showed high clinical activity and tolerability in heavily pretreated patients with relapsed/refractory B-cell non-Hodgkin lymphoma.<br /> &nbsp;

Heavily pretreated patients with relapsed/refractory B-cell non-Hodgkin lymphoma demonstrated antitumor activity when treated with varying dose levels of the human IgG4-based anti-CD20 &times; anti-CD3 bispecific&nbsp;monoclonalantibody, REGN1979.&nbsp;

An extended media overall survival of 9.9 months was achieved with CC-486 maintenance treatment compared with placebo for older patients with acute myeloid leukemia in first remission, according to findings from the phase III QUAZAR AML-001 trial presented at the 2019 American Society of Hematology Annual Meeting.<br /> <br /> &nbsp;

Ongoing benefits of 42 months were observed with Bruton&rsquo;s tyrosine kinase inhibitor acalabrutinib treatment in patients with relapsed/refractory chronic lymphocytic leukemia, according to long-term follow-up data from the phase I/II ACE-CL-001 study reported at the 2019 American Society of Hemetology Annual Meeting.

Stable disease status was achieved in patients with b-cell malignancies through treatment with &nbsp;vecabrutinib, a reversible, noncovalent Bruton&rsquo;s tyrosine kinase inhibitor, without producing any grade &ge;3 treatment-related adverse events, according to data presented at the 2019 American Society of Hematology Annual Meeting and Exposition.

<br /> Richard R. Furman, MD, professor of medicine, Morton Coleman, MD Distinguished Professor of Medicine, director, Chronic Lymphocytic Leukemia Research Center, Weill Cornell Medicine, and attending physician, NewYork-Presbyterian Hospital, discusses the 42-month follow-up data of acalabrutinib monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia.

Data from up to 6 years of long-term follow-up shows better progression-free survival, overall survival, objective response rates, and sustained efficacy for patients with chronic lymphocytic leukemia who receive single-agent ibrutinib in earlier lines of treatment, including those with high-risk prognostic factors. According to the poster presented by Paul M. Barr, MD, Division of Hematology/Oncology, Wilmot Cancer Institute, University of Rochester, Rochester, NY, during the 2019 American Society of Hematology Annual Meeting, first-line ibrutinib yielded deeper responses over time with 30% complete responses versus 10% to 12% CR for later lines of treatment.

Patients with high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma who previously progressed on ibrutinib, responded well to treatment the CD19-directed CAR T-cell therapy lisocabtagene maraleucel and had manageable toxicity, according to updated findings from the phase I/II TRANSCEND CLL 004 study presented at the 2019 American Society of Hematology Annual Meeting and Exposition.

The administration of a higher initial dose of duvelisib at 75 mg BID led to a higher overall response rate of 62% compared with 40% in patients with relapsed/refractory peripheral T-cell lymphoma who received 25 mg BID, according to data from the dose-optimization phase of the PRIMO trial presented at the 2019 American Society of Hematology Annual Meeting.<br /> &nbsp;

In the SEQUOIA trial, zanubrutinib, a Bruton&rsquo;s tyrosine kinase inhibitor, showed continued high overall response rates for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma, regardless of deletion 17p status, according to findings presented at the American Socitey of Hematology Annual Meeting and Exposition.

In the final analysis of the GADOLIN study in patients with rituximab-refractory indolent non-Hodgkin lymphoma, the combination of obinutuzumab plus bendamustine reduced the risk of progression or death by 43% compared with bendamustine alone. In patients with follicular lymphoma, the reduction was 49%.

Treatment with LOXO-305 prompted responses from more than half of patients with heavily pretreated B-cell malignancies, including patients with resistance or intolerance to other BTK inhibitors or BCL2 inhibitors, according to findings from the phase I/II BRUIN trial presented at the 2019 American Society of Hematology Annual Meeting and Exposition.

A 100% overall response rate was achieved with the combination of lenalidomide and obinutuzumab in patients with relapsed indolent non-Hodgkin lymphoma that was refractory to rituximab, according to findings of a single-arm, phase I/II trial presented at the 2019 American Society of Hematology Annual Meeting and Exposition.<br /> &nbsp;

Findings from a subgroup analysis of the phase III AUGMENT trial of patients aged 70 or older with indolent non-Hodgkin lymphoma showed a 34% reduction in the risk of disease progression or death compared with rituximab plus placebo, according data presented at the 2019 American Society of Hematology Annual Meeting and Exposition.<br /> &nbsp;

A high rate of rapid and durable complete responses were observed in patients with aggressive relapsed/refractory large B-cell lymphoma treated with lisocabtagene maraleucel.

In a phase I/II dose escalation study, there was a complete remission rate of 44% in patients with relapsed/refractory chronic lymphocytic leukemia receiving&nbsp;umbralisib, ublituximab, and venetoclax, according to findings presented at the 2019 ASH Annual Meeting.

Fixed-duration treatment with the combination of venetoclax plus obinutuzumab results in superior progression-free survival and high rates of undetectable minimal residual disease in patients with previously untreated chronic lymphocytic leukemia than chlorambucil plus obinutuzumab.

Patients with relapsed/refractory follicular lymphoma showed durable responses with the combination of polatuzumab-vedotin, obinutuzumab, and lenalidomide, according to results presented at the 2019 ASH Annual Meeting.

Obinutuzumab combined with lenalidomide resulted in early and very high complete response rates in previously untreated patients with follicular lymphoma in a single-center phase II study. At a median follow-up of 25 months, the 2-year progression-free survival was 96%.

An&nbsp;open-label, single-arm, phase II study in patients with&nbsp;chronic lymphocytic leukemia demonstrated the frontline AVO triplet, comprised of&nbsp;acalabrutinib, venetoclax, and obinutuzumab, achieved&nbsp;undetectable minimal residual disease in the bone marrow in 48% of patients after only 8 monthly cycles of therapy,&nbsp;according to lead author Benjamin L. Lampson, MD, PhD, who presented the findings at the 2019 ASH Annual Meeting.

Updated follow-up analysis of&nbsp;the phase III E1912 study showed that ibrutinib/rituximab induced higher rates of&nbsp;progression-free survival (PFS) when compared against fludarabine, cyclophosphamide, and rituximab in&nbsp;patients &le;70 years with previously untreated chronic lymphocytic leukemia (CLL), according to&nbsp;Tait D. Shanafelt, MD, who presented the findings at the 2019 ASH Annual Meeting.

Patients &lt;70 years old with&nbsp;chronic lymphocytic leukemia treated in the minimal residual disease (MRD)&ndash;cohort of the&nbsp;phase II CAPTIVATE trial had undetectable MRD rates of 75% and 72% in the peripheral blood and bone marrow, respectively, with the frontline&nbsp;combination of ibrutinib and venetoclax,&nbsp;according to findings presented at the 2019 ASH Annual Meeting.