Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia

In an interview with Targeted Oncology, Jeff P. Sharman, MD, discussed the updated ELEVATE-TN data and ongoing research that is poised to define the optimal role of acalabrutinib in CLL at the 2019 ASH Annual Meeting.

Jeff P.&nbsp;<a>Sharman</a>, MD, discusses the safety profile of acalabrutinib that was demonstrated in&nbsp;<a href="https://www.targetedonc.com/conference/ash-2019/patients-with-cll-treated-on-the-elevatetn-trial-experience-improved-pfs-with-acalabrutinib"><strong>the phase III ELEVATE-TN trial</strong></a>. The trial&nbsp;&nbsp;evaluated acalabrutinib&nbsp;&nbsp;as a single agent or in combination with obinutuzumab versus obinutuzumab&nbsp;&nbsp;plus chlorambucil in patients with treatment-na&iuml;ve chronic lymphocytic leukemia.

Following the 2019 ASH Annual Meeting,&nbsp;Targeted Oncology&nbsp;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.

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.

<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.

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 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.

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.

Jacqueline C. Barrientos, MD, MS, discusses&nbsp;exciting novel combination strategies that are being presented at the 2019 ASH Annual meeting.

Patients with&nbsp;treatment-na&iuml;ve chronic lymphocytic leukemia experienced&nbsp;a statistically significant improvement in progression-free survival with acalabrutinib as a single agent or in combination with obinutuzumab when&nbsp;compared with obinutuzumab plus chlorambucil,&nbsp;according to results from the phase III ELEVATE-TN trial presented at the 2019 ASH Annual Meeting.

When treatment decisions are being made regarding chronic lymphocytic leukemia (CLL), patient age should be an important factor. CLL is a disease of the elderly, with more than 40% of all patients &gt;75 years.

In November 2019, the FDA approved a number of treatments, including acalabrutinib for the treatment of chronic lymphocytic leukemia and small lymphocytic leukemia, as well as zanubrutinib for the treatment of mantle cell lymphoma. A biosimilar for pegfilgrastim was also approved under indications.

Thomas Kipps, MD, PhD, discusses the&nbsp;chronic lymphocytic leukemia treatment spectrum and the explosion of targeted therapies in the field.&nbsp;

Matthew S. Davids, MD, MMSc, discusses the rapid developments in the chronic lymphocytic leukemia treatment landscape.

The treatment spectrum for chronic lymphocytic leukemia has expanded significantly with the development and approval of several new agents.

The FDA has approved acalabrutinib for the treatment of adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma as either an initial or subsequent therapy.

Kanti R. Rai, MD, professor of medicine, Northwell Health and Zucker School of Medicine at Hofstra University, explains the importance of attention to age when treating patients with chronic lymphocytic leukemia, which is a typically elderly patient population.