Sandwich Treatment Model Shows Promise for Mantle Cell Lymphoma

Photo Credit: Design Cells

A sandwich treatment model that includes acalabrutinib and rituximab in combination with R-DHAOx chemotherapy shows encouraging results in phase 2 trial.

Current treatments for mantle cell lymphoma (MCL), which affects approximately 5% to 10% of all non-Hodgkin lymphoma patients, are not always curative, and there is a need for new and effective treatments. Although there have been significant advancements in treatment for MCL treatment, the disease remains challenging to treat due to its resistance to conventional chemotherapy and its tendency to relapse. The results of the WAMM trial (NHL33 ‘WAMM’ [ACTRN12619000990123]), a multicenter single-arm phase 2 clinical trial of acalabrutinib and rituximab in combination with dexamethasone, high-dose cytarabine, and oxaliplatin (R-DHAOx) chemotherapy for the treatment of MCL suggest a “sandwich treatment model” might be an innovative and effective approach, according to results presented at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition from December 9-12, 2023, in San Diego, California, and online. 

Physician’s Weekly (PW) spoke with the lead investigator, Eliza Hawkes, MBBS Hons, FRACP, DMedSc, from the Olivia Newton-John Cancer Wellness & Research Centre in Heidelberg, Australia, about how WAMM explored a novel approach to treating MCL through the use of acalabrutinib, a highly selective Bruton tyrosine kinase inhibitor (BTKi), in an innovative “sandwich” design. BTKis have improved first-line therapy efficacy in the elderly and young with MCL—the latter with intermittent dosing during RCHOP in an alternating RCHOP/cytarabine-based regimen.

The WAMM study included patients between the ages of 18 and 70 with previously untreated histologically-proven CD20-positive stage II-IV MCL (all subtypes). Eligible patients had an Eastern Cooperative Oncology Group performance status of 0-1 and no comorbidities that would preclude stem cell transplantation. The study evaluated the safety and efficacy of the acalabrutinib “sandwich” therapy. Specifically, the study assessed the rate of complete metabolic response (CMR) after induction therapy with acalabrutinib and rituximab, followed by R-DHAOx chemoimmunotherapy. 

Additionally, the study evaluates the overall response rate, overall toxicity, overall and progression-free survival, MRD negativity rates, and standardized quality of life scores. The WAMM study is expected to provide valuable insights into this novel approach’s potential to treat MCL and could lead to a paradigm shift in MCL therapy. The first results were presented at the 65th ASH Annual Meeting.

PW: Could you start by explaining the unmet needs in MCL?

Dr. Hawkes: MCL is a rare type of non-Hodgkin lymphoma. It’s classified as an indolent disease, which means that it progresses slowly. However, even though it’s classified as an indolent disease, the majority of people with MCL require some treatment. Traditional treatments for mantle cell lymphoma involve chemotherapy with rituximab. However, these treatments are not always effective and can cause significant side effects. In addition, MCL is rarely curable, and most patients will relapse. As a result, there is a clear need for new and better treatments for MCL. 

What are the goals of the WAMM trial, and how is it trying to fill unmet needs? 

The WAMM trial aimed to evaluate the efficacy and safety of a novel treatment approach for MCL. The treatment approach used in the WAMM trial involved a sandwiched treatment model, where the novel agent acalabrutinib was given in a window before and after standard chemotherapy. This approach aimed to improve outcomes by combining the benefits of the novel agent with the proven efficacy of standard chemotherapy while minimizing side effects. 

What was the primary endpoint of the trial? Did the results meet your expectations? 

The primary endpoint of the WAMM trial was the complete response rate (CRR) at the end of induction treatment. CRR is a measure of how well the treatment has worked. A complete response is defined as the absence of any signs or symptoms of cancer. In the WAMM trial, the CRR was 88%, which is significantly higher than the CRR of 77% seen in historical data. These results were very encouraging and exceeded our expectations.” 

The WAMM trial also evaluated the use of telehealth. What was the role of telehealth in the trial, and how did it impact recruitment? 

The WAMM trial was conducted in Australia, which is a large country with a relatively small population. This made it difficult for patients to travel long distances to receive treatment. To address this challenge, the WAMM trial used a hub and spoke telehealth model. The hub sites were responsible for delivering the more intensive aspects of the treatment, such as transplantation and chemotherapy. The spoke sites provided local care and support to patients. This model allowed the trial to recruit patients from all over Australia, including rural and remote areas. It also allowed patients to receive treatment closer to home, which reduced their travel burden and improved their quality of life.” 

Overall, what are your thoughts on the results of the WAMM trial? 

The results of the WAMM trial are very promising. The sandwiched treatment model with acalabrutinib showed excellent efficacy and safety. The telehealth hub-and-spoke model also successfully facilitated patient recruitment and improved access to care for patients in rural and remote areas. I believe these results can potentially transform the treatment of MCL.