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MCL treatment tool
Increasing Complexity in MCL Treatment Decisions and the Value of Interactive Tools

Released: July 21, 2025

Expiration: January 20, 2026

Julie M. Vose
Julie M. Vose, MD, MBA
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Key Takeaways
  • CCO’s interactive treatment decision–support tool, developed with 5 experts in mantle cell lymphoma, provides expert guidance for healthcare professionals in an increasingly complex treatment landscape.

The treatment landscape for mantle cell lymphoma (MCL) has rapidly evolved in recent years, resulting in an increasingly complex array of therapeutic options for both first-line and relapsed/refractory settings. Current treatment strategies include a range of chemotherapy-based regimens and Bruton’s tyrosine kinase (BTK) inhibitor therapies. To support healthcare professionals (HCPs) in navigating these complexities, I collaborated with 4 other US-based lymphoma experts to develop an interactive treatment–decision support tool. This tool enables you to enter detailed patient case information and receive tailored treatment recommendations from each of the 5 expert contributors who consider critical factors, including disease stage, patient fitness, gene mutations, and previous therapies.

Since the tool’s launch in April 2025, 62 HCPs have used it to evaluate 87 patient cases. Approximately one half (47%) of those who responded sought guidance for specific patients in their practice, whereas the remainder were interested in expert recommendations for specific hypothetical case scenarios. Among those using the tool whose initial treatment plans differed from the expert recommendations, 62% decided to alter their therapeutic approach. Of note, 82% of the submitted patient cases involved newly diagnosed MCL, indicating a significant desire for guidance navigating the increasingly complex first-line therapy treatment landscape.

I highlight a few interesting case scenarios that illustrate existing differences in treatment choices between the expert panel and the HCPs using this tool.

Treatment Recommendations for a Newly Diagnosed Patient:
For rare instances of newly diagnosed stage I MCL eligible for radiation therapy (RT), all contributing experts unanimously recommend RT for effective disease control, with or without chemotherapy. Of significance, more than 1 in 3 responding HCPs who entered this case scenario were initially planning observation-based strategies or were uncertain about their treatment decision, but all were convinced to change their treatment choice based on the tool showing consensus among the expert panel.

In scenarios where RT is not feasible or for later stage disease, most experts recommend treatment regimens incorporating covalent BTK inhibitors, tailored based on individualized patient risk factors. For example, consider a 75-year-old woman presenting with 3 months of enlarging lymph nodes, fatigue, and weight loss, leading to a diagnosis of stage III MCL. The workup shows she has no TP53 mutations and classic morphology, but she has high Ki-67 levels of 55% and FISH reveals complex cytogenetics. She also has a history of mild chronic kidney disease, osteoarthritis, and hypertension. For this patient, there is a consensus among the experts on this tool that the recently approved ECHO trial regimen of acalabrutinib plus bendamustine and rituximab (BR) is the best approach to treatment. Three experts specifically recommend acalabrutinib and a fourth recommends any covalent BTK inhibitor plus BR. Maintenance therapy with a covalent BTK inhibitor with or without rituximab is also recommended. Alternatively, rituximab with bendamustine and cytarabine (R-BAC) has shown sustained efficacy in older patient populations. However, R-BAC had significantly shorter PFS in patients with high Ki-67 levels than in those with low Ki-67 levels, so it may have limited efficacy for this patient.

Treatment Recommendations for a Relapsed/Refractory Patient:
For relapsed or refractory disease, expert recommendations depend on the prior therapies the patient had received and time to relapse after first-line therapy and patient fitness, emphasizing the importance of personalized treatment approaches. Now let us discuss a 60-year-old woman who originally presented with fever and rash to a local emergency room. During the workup, she was found to have splenomegaly and an elevated white blood cell count, specifically an elevated lymphocyte count. Flow cytometry results of a peripheral blood sample were consistent with MCL. The patient received CIT with BR to start. She completed 6 cycles of therapy and achieved complete remission at the end of treatment, after which she began receiving maintenance rituximab. She remained in remission for just <1 year, when she was noted on imaging to have recurrent disease after self-palpating a new node in the left groin.

Because of her early relapse after what would be considered a sufficient chemotherapy backbone in the frontline, I would be concerned about high-risk genetic features like TP53 mutation and I would now treat with a covalent BTK inhibitor. HCPs entering this case, or any BTK inhibitor–naive patient case, into the treatment decision support tool will find a consensus among the experts that optimal second-line treatment would be a covalent BTK inhibitor. Additional comments from some experts suggest that the addition of venetoclax could be considered as supported by the phase III SYMPATICO study and CAR T-cell therapy may be a subsequent third-line treatment.

In cases of relapsed or refractory disease without prior BTK inhibitor exposure, 85% of HCPs already intend to use covalent BTK inhibitors for their next treatment. However, expert guidance was most useful for nuanced newly diagnosed MCL and for relapsed/refractory disease after prior exposure to covalent BTK inhibitors. In the latter case, 80% of HCPs intended to use treatments that diverged from the expert consensus favoring CAR T-cell therapy, pirtobrutinib (a noncovalent BTK inhibitor) or approved bispecific antibodies.

I hope that you find this interactive treatment decision–support tool valuable for understanding how specific patient factors and current evidence shape expert treatment choices for the management of MCL.

Your Thoughts
What resources do you use when making treatment decisions for patients with MCL? Have you used a treatment decision–support tool when considering therapy for your patients? CCO also has a treatment decision–support tool that is focused on recommendations for the management of adverse events related to BTK inhibitor therapy. Try our latest tool for MCL treatment at clinicaloptions.com/MCLTool and our tool on BTK inhibitor adverse effect management at clinicaloptions.com/BTKitool. Let us know what you think with a comment in the discussion section below.

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