Rituximab induces effective clearance of minimal residual disease in molecular relapses of mantle cell lymphoma.
Molecular remission (MR) is associated with improved outcome in mantle cell lymphoma (MCL). If MR is not achieved, patients are at high risk of relapse. We retrospectively describe the molecular and clinical follow-ups of 4 patients with molecular relapses (M-rels) who were treated with rituximab. The 4 patients received rituximab-supplemented, high-dose sequential chemotherapy and autologous stem cell transplantation as induction treatment and achieved clinical remission and MR. M-rel was defined as polymerase chain reaction (PCR) positivity in 2 consecutive samples in the absence of clinical relapse. M-rels occurred at 3, 6, 39, and 52 months and were always confirmed by direct sequencing of the clonal rearrangement. Minimal residual disease was monitored by qualitative and real-time quantitative PCR. All patients received 4 courses of rituximab, with 2 additional infusions if PCR positivity remained. After 4-6 courses of rituximab, all patients re-entered MR. No clinical relapses were recorded at 3, 6, 18, and 62 months from treatment, although 1 patient had a second M-rel that was sensitive to rituximab. Our results indicate that rituximab is active against residual MCL cells and suggest that molecularly tailored maintenance therapy needs to be investigated in clinical trials.
Ladetto
Marco
M
Divisione di Ematologia, Dipartimento di Medicina ed Oncologia Sperimentale, Università di Torino, Torino, Italy. marco.ladetto@unito.it
Magni
Michele
M
Pagliano
Gloria
G
De Marco
Federica
F
Drandi
Daniela
D
Ricca
Irene
I
Astolfi
Monica
M
Matteucci
Paola
P
Guidetti
Anna
A
Mantoan
Barbara
B
Bodoni
Chiara Lobetti
CL
Zanni
Manuela
M
Boccadoro
Mario
M
Gianni
Alessandro M
AM
Tarella
Corrado
C
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics / Q000648:ultrastructure; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics / Q000648:ultrastructure; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004341:Drug Evaluation; D005500:Follow-Up Studies; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D018365:Neoplasm, Residual; D036102:Peripheral Blood Stem Cell Transplantation; D016133:Polymerase Chain Reaction; D011241:Prednisone / Q000008:administration & dosage; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D000069283:Rituximab; D016879:Salvage Therapy; D014178:Translocation, Genetic; D014182:Transplantation, Autologous; D014750:Vincristine / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007143:Immunoglobulin Heavy Chains; D003561:Cytarabine; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D008942:Mitoxantrone; D008558:Melphalan; D011241:Prednisone