The role of Maintenance Rituximab (MR) to improve progression free survival (PFS) following first line induction chemotherapy in low grade Non Hodgkins Lymphoma (NHL) has been evaluated in various trials. Ten year follow up data of the PRIMA trial has shown 51% patients in maintenance arm continued to be disease free as opposed to 35% in observation arm. MR was reportedly well tolerated; however the recent GALLIUM trial reported more frequent toxicity with Bendamustine induction chemotherapy.
We present below our experience of MR tolerance in low grade NHLs commenced on or already on MR in our unit between April 2014-August 2018(51 months)
129 patients with low grade NHL in complete (CR) or partial (PR) remission following first line induction chemotherapy(R-CHOP/R-Bendamustine/R-CVP/R-Chlorambucil/R-GCVP) went on to receive subcutaneous MR every two months for twelve doses. Data on toxicity, safety and tolerability was collected from patient records. At analysis, 44 patients still undergoing MR were excluded from further evaluation. 85 patients no longer on MR were evaluable. Of these, 6 patients stopped MR due to reasons unrelated to toxicity or progressive disease (patient choice, poor compliance etc) and were excluded from further analysis. Of the 79 patients analysed, 32 patients were in PR and 47 in CR as assessed by imaging and/or bone marrow examination at end of induction chemotherapy.
Of the 79 patients evaluated 71% (n = 56) completed 12 doses of MR and continued to be in remission (assessed by symptoms and clinical exam) at analysis. The remaining 29% (n = 23) had to discontinue MR. 20.2% (n = 16) discontinued due to toxicity (neutropenia, recurrent infections including neutropenic sepsis, hypogammaglobulinemia, intractable diarrhoea). 8.8% (n = 7) had progressive disease, MR was discontinued and they went on to receive other treatments. The PFS of the cohort evaluated was 79.6% at 45 months of follow up. Of the 79 NHL patients, 53 patients had follicular lymphoma in first remission. In this sub group 73.6% (n = 39) completed all 12 doses and were in remission at analysis, 17% discontinued due to toxicity (n = 9), 9.4% developed progressive disease (n = 5) and MR was discontinued.
Further analysis on whether induction regimen affected MR tolerability was undertaken. Of the 79 patients (low grade NHL's) analysed, 69 patients were treated with non Bendamustine containing induction regimen. Within this sub group 74% (n = 51) completed 12 doses of subcutaneous MR with no significant associated toxicity. However of the 10 patients who received R-Bendamustine as induction chemotherapy 50% (n = 5) had to discontinue MR due to associated toxicity. In our subgroup of follicular lymphoma in first remission (n = 53) 3.7% (n = 2) received R-Bendamustine containing induction regimen and neither were able to tolerate all 12 doses of MR.
Our data suggests that overall, MR is well tolerated in patients with low grade NHL with > 70% of patients experiencing minimal or no toxicity. It was however notable that MR was less well tolerated in patients who had prior Bendamustine containing induction chemotherapy, although our patient numbers treated with this agent at induction are not large enough for this observed adverse trend to be of statistical significance. It is noteworthy that the induction regimens assessed in the PRIMA trial did not include Bendamustine. A prospective trial to assess tolerability vs efficacy of MR following Bendamustine containing induction chemotherapy would provide more answers.