Mantle Cell Lymphoma

In an interview with&nbsp;<em>Targeted Oncology</em>, Simon Rule, MD, PhD, professor of Hematology at Plymouth University Medical School, United Kingdom, discusses the current treatment paradigm for MCL, as well as the potential use of BTK inhibitors for the treatment of this patient population.

Axicabtagene ciloleucel (axi-cel; Yescarta) has been approved by the European Commission as a treatment for&nbsp;adult patients with relapsed/refractory diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma, following at least 2 lines of systemic therapy.&nbsp;

Tisagenlecleucel has gained approval from the European Commission as a treatment for adult&nbsp;patients with diffuse large B-cell lymphoma that is relapsed or refractory after 2 or more lines of systemic therapy, or patients up to 25 years of age with B-cell acute lymphoblastic leukemia that is refractory, in relapse posttransplant, or in second or later relapse.

Mutations of <em>TP53</em> and <em>WHSC1 </em>predicted poorer overall survival in patients with mantle cell lymphoma, according to results from next-generation whole-exome sequencing of 16 Chinese patients.&nbsp;The presence of these mutations may provide physicians with an important biomarker in this patient population.

Targeting EZH2, the catalytic subunit of the multiprotein PRC2, may represent an attractive therapeutic objective in malignant lymphoma, Vincent Ribrag, MD, told his audience at the American&nbsp;Association for Cancer Research&rsquo;s inaugural Advances in Malignant Lymphoma meeting.

Brad Kahl, MD,&nbsp;discusses the exciting new advancements on the horizon for the treatment of patients with MCL.

Andre Goy, MD, shares insight on the new array of treatment options for mantle cell lymphoma and how to properly implement them.

Mogamulizumab-kpkc&nbsp;(Poteligeo) has been approved by the FDA as a treatment for patients with cutaneous T-cell lymphoma who have received at least 1 prior systemic therapy.

Patients with relapsed/refractory mantle cell lymphoma (MCL) who experienced progression of disease within 2 years following an upfront chemoimmunotherapy regimen containing high-dose cytarabine were more likely to have worse outcomes than patients who progressed later, according to the results of a retrospective analysis presented at the 2018 European Hematology Association Congress. Alternatively, patients who experienced POD later had an unexpectedly long life expectancy.

The addition of bortezomib to rituximab as a maintenance therapy following consolidative autologous hematopoietic stem cell transplantation may improve disease-free survival and overall survival in patients with mantle cell lymphoma, results of a small phase II study suggest.

The combination of ibrutinib (Imbruvica) and rituximab (Rituxan) produced durable remissions in patients with relapsed/refractory mantle cell lymphoma, according to 4-year follow-up results from a single-arm phase II clinical trial.

Maintenance rituximab improved progression-free survival and overall survival following induction chemoimmunotherapy for&nbsp;patients with mantle cell lymphoma, according to results of a recent meta-analysis.<br /> &nbsp;

Michael Wang, MD, discusses what he hopes to find in the ZUMA-2 trial and his belief that MCL can be cured in his lifetime.

An overall response rate of 60% was induced with venetoclax (Venclexta) monotherapy in&nbsp;patients with poor-risk relapsed/refractory mantle cell lymphoma who were previously treated with&nbsp;a BTK inhibitor,&nbsp;according to results presented at the 2018 European Hematology Association Congress.&nbsp;Of the responding patients, 20% had a complete response.

In patients with untreated advanced-stage classical Hodgkin lymphoma, PET can be safely used to&nbsp;guide treatment after 2 cycles of&nbsp;upfront de-escalated BEACOPP, according to the final analysis of the&nbsp;phase III LYSA study presented at the 2018 European Hematology Association Congress.

The 16-gene Leukemic-MCL16 (L-MCL16) Assay reliably distinguished between classic and indolent mantle cell lymphoma subtypes in patients with leukemic presentation, according to results published in <em>Blood</em>. Combined with genomic complexity, the assay was prognostic for overall survival.

The biggest clinical unmet need in the treatment of patients with mantle cell lymphoma is overcoming resistance to BTK inhibitors, as patients who progress on treatment with ibrutinib&nbsp;(Imbruvica) and acalabrutinib (Calquence) are often incurable, according to Michael Wang, MD. Investigators are now challenged to find a new avenue of treatment.

Pembrolizumab (Keytruda) has been granted&nbsp;an accelerated approval by the FDA&nbsp;for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or those who have relapsed after 2 or more prior lines of therapy.&nbsp;The approval is based on results from 53 patients with relapsed/refractory PMBCL enrolled in the multicenter, open-label, single-arm KEYNOTE&#8209;170 trial.

An objective response rate was achieved in 18 of 37 patients with&nbsp;relapsed/refractory non-Hodgkin lymphoma who received the combination of&nbsp;the BTK inhibitor ibrutinib with the PI3K inhibitor buparlisib, according to findings of a phase I/II trial&nbsp;reported at the 2018 ASCO Annual Meeting.

In an interview with&nbsp;<em>Targeted Oncology, </em>Andrew M.&nbsp;Evens, DO, MSc, discusses the clinical trials that are ongoing at Rutgers for patients with mantle cell lymphoma. He shares some details of the current treatment landscape and how that will evolve as more data becomes available from trials like those at his institution.&nbsp;

Expression of genes from the B-cell receptor pathway predicted shorter progression-free survival and overall survival in patients with mantle cell lymphoma, according to results from an examination of a subsection of patients in the ongoing Fondazione Italiana Linfomi MCL-0208 clinical trial.

Palbociclib, a CDK4/6 inhibitor, has demonstrated success against ibrutinib resistance in primary human samples and mantle cell lymphoma cell lines with the mutated BTKC481S protein. Its use has sparked an investigation of combination therapies targeting CDK4 in MCL, said Selina Chen-Kiang, PhD.

Based on data from the phase II JULIET study, tisagenlecleucel has received FDA approval for the treatment of&nbsp;adult patients with relapsed/refractory large B-cell lymphoma&mdash;including diffuse large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma&mdash;after 2 or more lines of systemic therapy.

While relapsed/refractory mantle cell lymphoma (MCL) is considered an aggressive disease, new findings show patients may benefit from adding chimeric antigen receptor T-cell therapy to their treatment regimen. ZUMA-2, a currently ongoing trial, aims to understand the potential benefits with axicabtagene ciloleucel, an&nbsp;anti-CD19 CAR T-cell product, for&nbsp;patients with relapsed/refractory MCL.

Voxtalisib (XL765) monotherapy induced objective responses in 41.3% of patients with follicular lymphoma, but displayed minimal efficacy in patients with other lymphomas, according to results from a phase II trial of patients with relapsed or refractory lymphoma or chronic lymphocytic leukemia that were recently published in the Lancet Haematology.