Safety of Bendamustine Monotherapy in CLL Patients with Concomitant Chronic Renal Failure

Abstract 4592

The optimal treatment of patients with chronic lymphocytic leukemia (CLL) and concomitant renal impairment is unclear. Fludarabine containing regimens are contraindicated in patients with glomerular filtration rate less then 30 ml/min. Alkylating agents are either contraindicated or require dose reduction due to their relatively large renal clearance. Treatment choice is especially difficult in cases with refractoriness to alkylating drugs. The aim of this study was to assess safety and efficacy of bendamustine monotherapy in CLL patients with concomitant chronic renal failure.

Seven patients with proven diagnosis of CLL and chronic kidney disease were treated with bendamustine monotherapy. The median age of patients was 66 years (range 61 – 83). All patients were males. The median creatinine level was 183 mkmol/L (range 165 – 573), the median level of glomerular filtration rate was 39 ml/min (range 23 – 47). The causes of chronic renal failure: membranous proliferative glomerulonephritis and focal CLL infiltration – 1 case, nephrectomy for cancer and massive CLL infiltration – 1 case, nephrectomy for cancer and pyelonephritis of sole kidney – 1 case, massive diffuse CLL infiltration with no other causes identified – 1 case, drug associated tubulointerstitial nephritis with development of irreversible renal failure – 1 case, chronic gout and urolithiasis in 1 case, unknown – 1 case. None of the patients required hemodialysis. Treatment consisted of bendamustine monotherapy, administered for two days every 4 weeks. Treatment in all patients started with dose 70 mg/m2/day. If the first course was well tolerated the dose was escalated to 100 mg/m2 on the next courses.

Three patients were newly diagnosed and four patients had relapsed disease, after a medium of 2 lines of therapy (range 1 – 2). Two patients were refractory to alkylating drugs. Before initiation of bendamustine 4 patients had Binet stage C, and 3 Binet stage B. Four patients received all planned 6 cycles of therapy with dose escalation to 100 mg/m2/day. In three patients treatment was stopped prematurely. In one patient treatment was discontinued after the 4th cycle because of the grade III skin rush and grade II polyneuropathy. One severely cardio compromised patient of 72 years developed grade III bradicardia after first cycle, requiring installation of cardiac pacemaker. One patient of 83 years with refractoriness to previous treatment died after 2 cycles from infectious complications. Neutropenia grade III was observed in 5 cycles in 3 patients. Aggravation of thrombocytopenia (grade II) was observed in 2 patients and aggravation of anemia (grade I) in 3 patients. In no case there was worsening of renal function. Decrease of creatinine and urea level was observed in 5 patients. Response can be evaluated in 5 patients. 2 patients achieved a nodular PR, and 3 patients achieved a PR.

In conclusion, monotherapy with bendamustine can be safely used in patients with CLL and renal impairment. Doses up to 100 mg/m2 are tolerated and do not cause worsening of renal function or severe hematological toxicity.