Interview: Sandwich treatment model shows promise for mantle cell lymphoma

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

Medicom Medical Publishers spoke with lead investigator Dr Eliza Hawkes (Olivia Newton-John Cancer Wellness & Research Centre, Australia) about how WAMM explores a novel approach to treating MCL, namely through the use of acalabrutinib, a highly selective Bruton’s tyrosine kinase (BTK) inhibitor, in a unique and innovative ‘sandwich’ design [1]. BTK inhibitors have improved first-line therapy efficacy in both elderly and young, fit, MCL; the latter with intermittent dosing during R-CHOP in an alternating R-CHOP/cytarabine-based regimen [2,3].

The WAMM study enrolled patients between the ages of 18 and 70 years with previously-untreated, histologically-proven, CD20-positive, stage II–IV MCL (all subtypes). Eligible patients were required to have an ECOG performance status of 0–1 and no comorbidities that would preclude stem cell transplantation (SCT). The primary goal of the WAMM study is to evaluate the safety and efficacy of the acalabrutinib sandwich therapy. Specifically, the study assesses 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, minimal residual disease (MRD) negativity rates, and standardised quality of life scores. The WAMM study is expected to provide valuable insights into the potential of this novel approach for the treatment of MCL and could potentially lead to a paradigm shift in MCL therapy. The first results were presented at the 65^th ASH Annual Meeting [1].

Could you just start by telling us a little bit about the unmet needs in MCL?

“MCL is a rare type of non-Hodgkin lymphoma and it is classified as an indolent disease, which means that it progresses slowly. Despite this, the vast majority of people with MCL do need some treatment. Traditionally, treatment for MCL has involved chemotherapy with rituximab, but these treatments are not always effective and can cause significant side effects. In addition, MCL is rarely curable, and most patients will relapse. Thus, there is a clear need for new and better treatments.”

What are some of the goals of the WAMM trial? How are you going about trying to fill that unmet need?

“The WAMM trial aims to evaluate the efficacy and safety of this novel treatment approach for MCL, involving a sandwich treatment model where acalabrutinib is given in a window before and after standard chemotherapy. The goal of this approach is to improve outcomes, combining the benefits of the novel agent with the proven efficacy of standard chemotherapy, while minimising 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. The 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 participants 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 were responsible for providing local care and support to participants. 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 first results of the WAMM trial are very promising. The sandwich treatment model with acalabrutinib showed excellent efficacy and safety. The telehealth hub-and-spoke model was also successful in facilitating patient recruitment and improving access to care for participants in rural and remote areas. I believe that these results have the potential to transform the treatment of MCL.”

1. Hawkes E, et al. A Window Study of Acalabrutinib & Rituximab, Followed By Chemotherapy & Autograft (ASCT) in Fit Patients with Treatment Naïve Mantle Cell Lymphoma (MCL): First Report of the Investigator-Initiated Australasian Leukaemia & Lymphoma Group NHL33 ‘Wamm’ Trial. Abstract 735, 65^th ASH Annual Meeting, 9–12 December 2023, San Diego, CA, USA.
2. Wang ML, et al. N Engl J Med. 2022 Jun 30;386(26):2482-2494.
3. Hermine O, et al. J Clin Oncol. 2023 Jan 20;41(3):479-484.

 

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Posted on 4 January 202421 March 2024