Chronic Lymphocytic Leukemia

The combination of venetoclax with rituximab led to high rates of undetectable minimal residual disease for patients with relapsed/refractory chronic lymphoblastic leukemia. This was associated with a prolonged progression-free survival, according to a new analysis of a randomized trial presented at the 2018 ASH Annual Meeting.

The BTK inhibitor acalabrutinib demonstrated promising reponse rates in patients with newly diagnosed or relapsed/refractory chronic lymphocytic leukemia, according to results from an open-label phase II trial.

During a recent&nbsp;<em>Targeted Oncology&nbsp;</em>case-based peer perspective presentation, William G. Wierda, MD, PhD, revealed the treatment options and decisions he makes when treating patients with chronic lymphocytic leukemia. Wierda explained his treatment decisions based on a patient&rsquo;s case scenario.

Although there were a variety of encouraging data presented at the 2018 ASH Annual Meeting, CLL and multiple myeloma undoubtedly ruled the day, according to poll results. As these topics heated up on Twitter, a few experts took a moment to discuss their thoughts on some of the top abstracts that were presented.

A newly discovered recurrent mutation in the&nbsp;B-cell leukemia/lymphoma 2 protein&nbsp;in patients with chronic lymphocytic leukemia has been linked to venetoclax resistance.

Venetoclax monotherapy induced high rates of minimal residual disease in the peripheral blood and bone marrow in patients with&nbsp;relapsed/refractory chronic lymphoblastic leukemia in a pooled analysis of 2 clinical trials. Data from the analysis was reported during the poster session at the 2018 ASH Annual Meeting.

A significant reduction in the risk of&nbsp;disease progression or death was observed from treatment with the upfront combination of&nbsp;ibrutinib plus obinutuzumab in patients&nbsp;with chronic lymphocytic leukemia and small lymphocytic lymphoma compared with&nbsp;chlorambucil and obinutuzumab.&nbsp;

According to a presentation of findings from the&nbsp;phase II CLARITY study at the 2018 ASH Annual Meeting, ibrutinib in combination with&nbsp;venetoclax demonstrated tolerability among patients with relapsed/refractory chronic lymphocytic leukemia. The combination also induced minimal residual disease negativity in the marrow in&nbsp;39% of these patients after 12 months.

Pembrolizumab in combination with&nbsp;umbralisib and ublituximab induced responses in 90% of patients&nbsp;with&nbsp;relapsed/refractory chronic lymphocytic leukemia, according to data from a phase I/II study presented at the&nbsp;2018 ASH Annual Meeting. Additionally, a&nbsp;50% response rate was also demonstrated in patients with&nbsp;Richter&rsquo;s transformation.

After 7 years of follow-up, single-agent ibrutinib demonstrated continued efficacy in&nbsp;the frontline and heavily pretreated, relapsed/refractory settings for patients with&nbsp;chronic lymphocytic leukemia and small lymphocytic lymphoma.

Lisocabtagene maraleucel induced an 81.3% best overall response rate and 43.8% complete response in high-risk patients with&nbsp;chronic lymphocytic leukemia who were heavily pretreated and had previously received ibrutinib, according to dose-finding results presented at the 2018 ASH Annual Meeting.&nbsp;

According to a retrospective phase I/II study, over 80% of patients with relapsed or refractory chronic lymphocytic leukemia responded to concurrent treatment with ibrutinib and the CD19-targeted chimeric antigen receptor CAR T-cell therapy, JCAR014.¹ Findings from this study were presented at&nbsp;the 60th American Society of Hematology Annual Meeting.

According to updated data from the phase II ELIANA study,&nbsp;CD19-targeted CAR T-cell therapy tisagenlecleucel as treatment of&nbsp;pediatric and young adult patients with relapsed or refractory acute lymphoblastic leukemia sustained rates of&nbsp;relapse-free survival and overall survival at 24 and 18 months.&nbsp;

Progression-free survival was significantly improved with both ibrutinib as monotherapy and in combination with rituximab when&nbsp;compared to bendamustine plus rituximab as a treatment for older patients with newly diagnosed chronic lymphocytic leukemia. These data were presented at the 2018 ASH Annual Meeting.

Susan M. O&rsquo;Brien, MD, discusses the challenges with the 3 oral agents approved in chronic lymphocytic leukemia.

CLL is a malignant disease characterized by progressive accumulation of immature, immunophenotypically distinct lymphocytes in the blood, bone marrow, and lymphatic tissues. Although the clinical course of CLL can be unpredictable, this disease is typically slow-progressing and occurs most often in patients &ge;65 years of age.&nbsp;As such, treatment, if indicated, is typically conservative.&nbsp;Current CLL treatments are not considered to be curative; however, long-term remission can be achieved in some patients using allogenic stem cell transplantation.

Chronic lymphocytic leukemia is characterized by the clonal proliferation and accumulation of small, mature-appearing CD5-positive B lymphocytes in the blood, bone marrow, and secondary lymphoid tissues.&nbsp;A CLL diagnosis is established by the presence of more than 5x109/L peripheral lymphocytes co-expressing CD5, CD19, and CD23, and weakly expressing CD20, CD79b, and surface immunoglobulin.&nbsp;Small lymphocytic lymphoma represents a clinical variant of CLL and is similarly managed.

Richard Furman, MD, discusses how survival times for patients with chronic lymphocytic leukemia have increased dramatically in the past decade, thanks to an ever-expanding armamentarium of novel agents and more patients now being diagnosed earlier.

A look back at all the&nbsp;FDA news&nbsp;that happened in the month of&nbsp;October 2018, including several new FDA approvals, priority reviews, a breakthrough therapy designation, and more, in a variety of cancer types.<br /> &nbsp;

Treatment-na&iuml;ve patients with chronic lymphocytic leukemia who had comorbidities saw a reduction in the risk of disease progression or death after treatment with venetoclax combined with obinutuzumab versus obinutuzumab plus chlorambucil.

Sarah K. Tasian, MD, discusses what she finds most interesting about Philadelphia chromosome (Ph-like) acute lymphoblastic leukemia.

A&nbsp;supplemental new drug application for ibrutinib (Imbruvica) has been granted a priority review by the FDA&nbsp;for use in combination with obinutuzumab (Gazyva) as a frontline treatment for adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.

Danielle Brander, MD,&nbsp;discusses the current treatment landscape in the frontline setting for patients with chronic lymphocytic leukemia.

Shagun Arora, MD, discusses new agents and combination studies beyond chemoimmunotherapy for patients with CLL.

Mazyar Shadman, MD,&nbsp;discusses the evolution of therapy in CLL and how physicians are working to balance these novel agents with additional modalities.<br /> &nbsp;