Abstract
Introduction.
Mantle Cell Lymphoma (MCL) represents 5-7% of all non-Hodgkin Lymphomas (NHL) and is still an incurable disease. In recent years first line treatment approaches were strongly improved both for younger (i.e. high-dose cytarabine regimens) and for elderly patients (pts) (i.e. bendamustine-including regimens or Rituximab maintenance after RCHOP therapy). However, MCL retains a strong tendency to recurrence with shorter Duration of Response (DOR) after any further line of therapy. Furthermore, in recent years many drugs were developed, that have demonstrated strong efficacy in the treatment of relapsed/refractory (R/R) MCL. In particular, the BTK inhibitor Ibrutinib is currently used in the treatment of R/R MCL worldwide with the highest single-agent efficacy in terms of Overall Response (ORR) and Complete Response Rate (CRR) and DOR. With the wide use of Ibrutinib new problems are emerging, for example a certain aggressiveness of MCL relapsing after or resistant to this drug. Furthermore, some patients present one or more co-morbidities that preclude or at least contraindicate Ibrutinib treatment, especially atrial fibrillation or the needing for anti-coagulation. Finally, many treatments of R/R MCL are currently available (Bendamustine, Bortezomib, Lenalidomide, etc…) and there are no data suggesting which could be the more effective "treatment-sequence" for MCL pts. The proteasome inhibitor Bortezomib demonstrated its efficacy in the treatment of R/R MCL with good ORR and DOR, both as single drug and in association with Rituximab. However, due to rapid availability of new drugs, its role as a potential treatment of R/R MCL is under-explored, even if a good toxicity profile was also observed. Here we report our experience of Rituximab plus Bortezomib (R+B) as salvage therapy for pts with R/R MCL.
Materials and Methods.
We retrospectively analyzed a cohort of R/R MCL pts treated from January 2008 to December 2013 with the following regimen: i.v. Bortezomib 1.6 mg/m2 on days 1, 8, 15 and 22 of a 35-days cycle for 6 cycles; i.v. Rituximab 375 mg/m2 administered on the same treatment days for 2 cycles. The aims of this study are an analysis of efficacy (in terms of ORR, CRR, PFS, DOR, OS) and of (hematological and non hematological) toxicity. Response to treatment was evaluated by chest-abdomen and pelvis CT scan; for the evaluation of response Cheson 2007 criteria were applied. Patients also underwent bone marrow evaluation and endoscopy, if positive at baseline.
Results.
Nineteen pts were treated according to the R+B regimen. Pts' characteristics are summarized in table 1. A median of 4.5 cycles were administered (range 1-6).
Efficacy analysis . The ORR was 63% (12 pts) and the CRR was 53% (10 pts), while one pt experienced a stable disease and in the remaining 6 cases a progression of disease was observed. The median PFS and OS (Figure 1) were 32,6 and 45,7 months respectively, while median DOR was 28,6 months (with no significant differences between pts reaching CR or PR after treatment).
Toxicity analysis . Grade (g) 3-4 neutropenia was observed in 6/19 pts but no cases of FN were observed, even if 14/19 pts received some G-CSF prophylaxis. One pt with g3 anemia at the start of R+B treatment experienced g4 anemia and received multiple RBC support, while g3 and 4 thrombocytopenia were experienced by 3 pts and 1 pt respectively with no major bleeding events and no need for transfusions. The most frequent extra hematological toxicities were gastrointestinal (6 pts; all g1), neurological (5 pts; 3 g2 and 2 g1), asthenia (4 pts; 2 g2 and 2 g1), while 4 pts experienced infections (1 g1, 2 g2, 1 g3). Because of toxicity, 7 pts had a dose reduction (mainly related to neurological symptoms) and 9 pts experienced some delay in treatment administration or single-day treatment interruption. There were no deaths related to hematological or non-hematological toxicity.
Conclusion.
Even in the era of the new drugs for the treatment of R/R MCL, R+B still represents an attractive treatment option due to its high efficacy and its low toxicity profile and should be strongly considered in the armamentarium of MCL therapies that should be offered to our pts
No relevant conflicts of interest to declare.
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