Treatment options in patients with mantle cell lymphoma (MCL) https://www.m3india.in/contents/editor_pick/105496/treatment-options...

Treatment options in patients with mantle cell

lymphoma (MCL)
Summary

Mantle Cell Lymphoma due to its clinical heterogeneity requires clear interpretation of prognostic factors
to determine treatment options. In this CME, Dr. Vishwanath discusses evidence-based therapeutic
strategies for different case presentations of MCL.

Mantle cell lymphoma (MCL) is a relatively unusual non-hodgkin lymphoma with variable prognosis.
With the use of rituximab and intensive chemo-immunotherapy followed by autologous stem cell
transplant, there has been improvement in progression-free survival (PFS) and overall survival (OS) as
well. Even in transplant ineligible patients, less intensive chemotherapy and targeted therapy have
improved survival rates.

Discussed here is the management of patients with MCL based on case scenarios:

Case 1

A 65-year-old asymptomatic gentleman was found to have a WBC count of 65000/microlitre. On physical
exam, he had no significant lymphadenopathy. Ultrasound abdomen showed evidence of mild
splenomegaly and no enlarged lymph nodes (LN). Peripheral blood flow cytometry was diagnostic of
MCL. Bone marrow biopsy showed a Ki 67 of 20%. He had a hypermutated IGHV and TP53 was
negative.

What would the appropriate treatment be?

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1. Watch and wait

2. R-CHOP
3. Bendamustine with rituximab (BR)
4. Rituximab, Bendamustine with cytarabine
5. R-CVP

The right answer, in this case, would be (a).

A small percentage of patients with MCL have an indolent course. This patient is asymptomatic and has a
leukaemic, non-nodal presentation of MCL. This generally has an indolent course similar to CLL. Patients
with good PS, absence of B symptoms, with a normal LDH, low Ki 67 (<30%), SOX-11 negativity, TP53
negativity and a non blastoid morphology tend to have a superior overall survival with observation.

A retrospective single center study of 97 patients with MCL reported by Martin et al showed that 32% of
patients were observed for over 3 months before initiating systemic therapy and treatment was deferred for
more than one year in 14 patients and more than 5 years in three patients. [1]

Case 2

A 50-year-old male with no comorbidities presented with fever, fatigue, significant weight loss, and
abdominal pain. PET/CT showed a large conglomerate retroperitoneal lymph node (LN) with bilateral
axillary and cervical lymphadenopathy. His PS was 1. Cervical LN biopsy was diagnostic of MCL (non-
blastoid variant), LDH was 400 U/L, Ki 67 40% and biological MIPI score was 6.7 (high risk).

Which of the following treatment options may be considered the most appropriate?

1. BR followed by ASCT
2. R HyperCVAD/MTX-ARAC
3. Nordic regimen
4. RDHAP/R-CHOP followed by ASCT and maintenance rituximab
5. RCHOP followed by ASCT and maintenance rituximab
6. Any of the above

The answer is (f), but the best answer is (d).

Though any of the above options can be used in this case, this patient is young, fit, and with no co-
morbidities. He is symptomatic with a high MIPI score and transplant eligible. It would be appropriate to
give a high intensive chemo-immunotherapy regimen like R-DHAP alternating with R-CHOP (total 6
cycles) and consolidate with autologous stem cell transplant (ASCT) in CR1.

This was based on a randomised trial of 497 patients with a median age of 55 years comparing R-DHAP
alternating with R-CHOP (total 6 cycles) with R-CHOP x 6 cycles followed by high dose cytarabine
conditioned ASCT. At a median follow up of 6 years, R-CHOP/R-DHAP resulted in longer time to
treatment failure (median 9.1 Vs. 3.9 years). [2]

The addition of ASCT in CR1 improves PFS. [3] Other regimens like R-HyperCVAD alternating with
MTX/ARA-C without ASCT can also be used as an induction therapy as shown in a single-center
experience which resulted in a failure-free survival of 15 years in one-third of younger patients with MCL.
However, there was significant toxicity. [4]

The role of maintenance rituximab (3 years, every 2 months) after ASCT was addressed in the LYMA trial
which showed improvement in PFS and OS. [5]

However, there is limited role of rituximab maintenance following BR induction (Rummel, et al. ASH
2016) [6] and the use of BR induction in high-risk MCL is debatable.

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The role of minimal residual disease at the end of induction and utility of ASCT in patients with MRD
negativity following induction is evolving.

Note: The morphology here was non blastoid. Had it been a blastoid morphology, the treatment option in a
young, fit patient would be R-HyperCVAD alternating with MTX/ARA-C and possibly consolidation
auto/allo SCT. This patient should also receive intrathecal MTX apart from systemic MTX to prevent CNS
relapse which is more common in blastoid variants.

Case 3

An 80-year-old male presented with B symptoms and lower GI bleed due to colonic involvement by MCL.
His PS was 1. PET/CT also showed supra and infradiaphragmatic LN involvement with maximum LN
size of 4 x 4cm. Bone marrow showed involvement by MCL with Ki 67 of 30%.

Which of the following treatment options would be appropriate in him?

1. BR
2. R—CHOP
3. R-BAC
4. Rituximab with lenalidomide
5. Ibrutinib
6. a,b,c,b

The right options would be (a), (c) and (d).

Treating elderly patients with MCL is always a challenge. A comprehensive geriatric assessment taking
into account the comorbidities is a prerequisite. Using less intensive regimens is the key. BR as shown in
the StiL and the BRIGHT study is a reasonable regimen to adopt. [7,8]

R-BAC (bendamustine and cytarabine) with rituximab based on a phase II study which showed CR of
91% with 2 year PFS and OS of 81% may also be considered. However this regimen had significant
hematological toxicity and should be used with caution in elderly patients. [9] The combination of
Lenalidomide plus rituximab led to ORR of 92% and 5 year PFS of 64% and OS of 77% which is well
tolerated in elderly patients may be an option. [10]

Case 4

A 58-year-old woman was diagnosed with MCL, received 6 cycles of R-CHOP followed by ASCT and
maintenance rituximab. Two years later, she develops a relapse.

What would be the most appropriate treatment option?

1. Lenalidomide with rituximab

2. Ibrutinib
3. BR+/- Bortezomib
4. Chemo-immunotherapy followed by Allogeneic SCT
5. Any of the above

Here, it could be (e).

Any of the above options can be considered based on various patient factors like PS, co-morbidities and
fitness for allo SCT.

1. Lenalidomide with rituximab is an option for this patient. Wang and colleagues reported results in

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Treatment options in patients with mantle cell lymphoma (MCL) https://www.m3india.in/contents/editor_pick/105496/treatment-options...

52 patients with R/R MCL in a phase I/II trial. The ORR was 57% and the median PFS reported was
11.1 months. It is a well tolerated regimen and effective in R/R MCL. [11]
2. Single-agent Ibrutinib has modest activity in relapsed MCL and can be considered based on a phase
2 study of 111 patients with MCL. The ORR was 68% and median PFS was 13.9 months. [12]
3. In patients like the current one who have not been exposed to BR during induction, the combination
of BR with bortezomib is a reasonable option. The ORR was 71% and 2 year PFS was 47% in a
phase II study. [13]
4. Chemo-immunotherapy options like BR or R-DHAP followed by allogeneic SCT may be
considered. However, this patient is 58 year old and has had an ASCT before. Hence fitness for allo
SCT should be assessed prior to transplant.
5. Acalabrutinib, a BTK inhibitor is also an option. However, it is not available in India.

Click here to see references

Disclaimer- The views and opinions expressed in this article are those of the author's and do not
necessarily reflect the official policy or position of M3 India.

The writer, Dr. Vishwanath Sathyanarayan is a Medical Oncologist from Apollo Hospitals, Bangalore with
a fellowship in Lymphoma & Myeloma from MD Anderson Cancer Center.

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