TOXICITY PROFILE DURING TREATMENT WITH BENDAMUSTINE-BORTEZOMIB-DEXAMETHASONE IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA

Background:

Treatment with bendamustine-bortezomib-dexamethasone (BBD) exerts significant activity in patients with relapsed/refractory multiple myeloma even in those pretreated with bortezomib or lenalidomide or both, but may be associated with clinically relevant side effects.

Aims:

Here we analyze the side effect profile with specific emphasis on infections, cytopenias and neuropathy in patients enrolled in a trial with BBD for relapsed/refractory multiple myeloma.

Methods:

Seventy-nine patients with relapsed/refractory MM have been enrolled. Median age: 64 years (range 40-86), male/female: 37/42, ISS stage I/II/III: 27, 31, and 21, respectively. ECOG status 0-I/≥II: 75, and 4 patients, respectively. Previous treatment lines: 1-2: 50, 3-4: 23, >4: 6 patients, respectively. Treatment regimen: bendamustine 70 mg/m² day 1+4, bortezomib 1.3 mg/m² days 1, 4, 8 and 11, dexamethasone 20 mg on days 1, 4, 8 and 11, repeated every 4 weeks. Planned number of treatment cycles was 8, with discontinuation after 4 cycles in case of no response. Toxicity grading was performed using the CTC v 3.0 scale. The FACT-GOG/NTX instrument was used for patients self-assessment of neuropathic side effects.

Results:

G3/4 infections were noted in 16 (20%) patients and 2 patients died due to infection/sepsis (G5). Low baseline ANC (<2.800/ml), a higher number of cycles (>4 cycles), and age >65 years showed a weak, but statistically non-significant correlation with G3/4 infections.

G3/4 thrombopenia was recorded in 28 (35%) patients; 18 of them presented with more than one episode (median: 3, range 2-8). Severe thrombopenia resulted in treatment discontinuation in 2, and in delay of therapy in 7 patients, respectively. Lower baseline platelet levels (<182.000/µL) were associated with higher risk for G3/4 thrombopenia (p<0.021).

Peripheral neuropathy assessed by the clinical care team was reported in 44 (56%) patients. G3/4 neuropathy was observed in 5 patients only. The occurrence of neuropathy increased, albeit not statistically significant, with increasing number of treatment cycles. Self-assessment of neuropathy by patients revealed a much higher PNP incidence with G1/2 PNP reported  by 37 (47%) and G3/4 PNP reported by 38 (48%) patients. Pretreatment with bortezomib or thalidomide, or both bortezomib and thalidomide was not associated with higher incidence of G3/4 PNP.

Summary / Conclusion:

Low baseline ANC and were associated with a higher risk for G3/4 neutropenia (p<0.012) and low baseline platelets counts were associated with G3/4 thrombopenia (p<0.021). Lower baseline ANC levels correlated with shorter PFS (p<0.01). Higher age, longer therapy and low baseline ANC tended to correlate with G3/4 infections. Furthermore, incidence of G3/4 neuropathy was low, but increased slightly with increased treatment duration. In stark contrast to evaluations by care givers, a much higher incidence of PNP was revealed when patients graded the incidence and severity of PNP by using a self-assessement instrument. Physicians should be aware of the substantial underrating of PNP by health professionals.

Abstrakta v časopise Haematologica 2013, Suppl1

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