Table 3 Summary of ALSG recommendations

Indolent MCL

• Adoption of a management strategy similar to CLL, utilizing a “watch-and-wait” approach, may be appropriate for asymptomatic patients with MCL. Typical clinical presentation of indolent disease comprises leukemic non-nodal CLL-like, including low tumor burden and Ki67 proliferation fraction < 10%. It is useful to confirm SOX11 negativity with hypermutated IGHV to determine clearly indolent disease.

• Patients are often reluctant to undertake a “watch-and-wait” strategy. For asymptomatic patients desiring treatment, the same treatment scheme for symptomatic patients requiring treatment is considered.

• Communication between the clinician and the patient, as well as the patients’ family members or caregivers, in the decision-making process is recommended.

• Clinical trial enrollment is strongly suggested where possible.

Stage I/II limited, non-bulky disease

• Following ESMO and NCCN guidelines is appropriate for Asian MCL patients.

• However, consideration could also be made to treat according to guideline recommendations for advanced disease, particularly if there are adverse histological features.

Advanced stage: young, fit patients

• Current practice for induction therapy in young fit patients differs across Asia based on drug availability and reimbursement status.

• Few physicians use HyperCVAD; however, this risks omitting or reducing the dose of cytarabine, which may be the most useful drug.

• Cytarabine has an important role as induction therapy in MCL but there is a lack of data supporting the best cytarabine dosage and dosing interval.

• The interaction between cytarabine and purine analogs should be considered to address concerns around cytarabine dose and toxicity.

• Clinical trial enrollment is strongly suggested where possible.

Advanced stage: elderly, unfit patients

• Choice of therapy in Asia is limited by drug availability and reimbursement status.

• R-CHOP, R-BAC, CHOP, and VR-CAP are used in this setting in Asia. BR is the preferred regimen in elderly, unfit patients.

• Bendamustine is associated with lower CD4 counts and an increased risk of infection. These risks must be monitored closely when considering this agent and prophylaxis for pneumocystis pneumonia should be considered.

• Clinical trial enrollment is strongly suggested where possible.

Role of HSCT

• Some ALSG members felt that the high chance of relapse within 3–4 years, even with consolidation therapy, may justify ASCT in young fit patients. While the recommendation that all responding patients should receive ASCT has become generally accepted, this remains uncertain, especially with novel agents changing the therapeutic landscape. Therefore, for young women of reproductive age, ASCT should be avoided and in relatively older individuals for whom reproduction is not a concern, ASCT remains an important option.

• In most Asian countries, HSCT is reimbursed by payors, whereas novel therapies are not; the decision for transplant may be financially driven rather than data-driven. However, real-world data may demonstrate the role or benefit of auto-SCT in some patients.

• Whether high-dose therapy followed by ASCT can be safely omitted from intensive first-line therapy that incorporates a BTK inhibitor will be tested in a European clinical trial.

Maintenance therapy after first-line treatment

• The clinical benefit of rituximab-maintenance therapy following BR and VR-CAP is not convincing.

• Rituximab-maintenance therapy should be recommended after R-CHOP or cytarabine-containing induction therapy.

• The choice of rituximab-maintenance therapy in Asian patients should be individualized, and affordability and reimbursement status remain important considerations in the region.

Relapsed/refractory treatment

• Ibrutinib should be considered in the second rather than later-line setting.

• Ibrutinib is tolerable in Asian patients. Adverse events (e.g., non-specific musculoskeletal symptoms, skin dryness or itching, changes to nails and hair) are not well characterized in the literature, and more Asian real-world data might be needed.

• Follow-on BTK inhibitors including zanubrutinib could be considered if available, but a difference to ibrutinib in terms of efficacy and safety remains to be shown.

• Clinical trial enrollment is strongly suggested where possible, especially for patients with TP53 mutation associated with poor prognosis.