Mantle cell lymphoma (MCL) has a low complete response (CR) rate
(21%) after anthracycline-containing regimens, a short duration of response
(median: 10 months), and dismal survival (median: 2 to 4 years). This improves
to 100% after hyper CVAD (cyclophosphamide [Cytoxan, Neosar],
vincristine/doxorubicin [Adriamycin], dexamethasone) alternating with high-dose
methotrexate and ara-C (hyper CVAD/M-A) consolidated with high-dose chemotherapy
with stem cell rescue and total-body irradiation (HDCT-SCT/TBI) (J Clin Oncol
In this study, seven patients did not receive transplant because
of financial reasons, inability to harvest stem cells, or refusal. Instead, they
received up to eight cycles of hyper CVAD/M-A, achieving CR after six cycles.
Because of this, we are currently investigating eight alternating cycles of
hyper CVAD/M-A in previously untreated patients but without consolidation with
HDCT-SCT/TBI unless a CR is not achieved after the first six cycles of
treatment. We have included rituximab (Rituxan) at
375 mg/m2 given 24 hours before each of the first six cycles of therapy.
Infection prophylaxis was as in the previous report.
As of July 2000, 43 patients have been entered in the study and
37 are eligible for response. Of these, 1 died after cycle 2 (M-A) for unclear
reasons. The remaining 36 patients all responded, making the response rate 97%.
Eight of these achieved partial response (PR) and are still responding to
therapy, 1 achieved a stable PR, and 27 are in either CR (24 patients) or CRu (3
patients). A total of 29 patients have completed at least 6 cycles, 28 of whom
(97%; one death) have achieved a response and 26 of whom (90%) are complete
responders. Of the two partial responders, one patient is over 65 years old and,
by protocol requirements, received only one-third of the ara-C dose. The other
patient had stable partial response but refused consolidation with HDCT-SCT/TBI
and is now progressing.
With a median follow-up of 8 months, 2/37 (5%) patients have
failed (one death, one PR who progressed). This contrasts with 14/28 (50%)
relapse rate at 8 months median follow-up for the historical CHOP
(cyclophosphamide, doxorubicin HCl, vincristine [Oncovin], prednisone) control
group (P = .001), and is comparable to the failures for the transplanted group
in the prior study at 8 months of follow-up (4%). As expected, hematologic
toxicity was severe but only 8% of patients developed grade 3 infection and none
developed grade 4 infection by National Cancer Institute criteria.
CONCLUSION: Our results are encouraging and the trial continues
to accrue patients.