Expanding Role of Bortezomib in Multiple Myeloma: Nursing Implications

Kathleen Colson, RN, BSN, BS; Deborah S. Doss, RN, OCN; Regina Swift, RN, BSN; Joseph Tariman, RN, APN, MN, BC, OCN

Disclosures

Cancer Nurs. 2008;31(3):239-249. 

In This Article

Special Populations

Depending on the treatment regimen used, patients with renal impairment may achieve lower response rates[41,42] and shorter overall survival,[41,42] and there may be greater safety concerns, thus necessitating a lower dose.[43] For optimal activity, delivery at full dose of an effective treatment is an important goal in these patients.[44] An analysis of patients with impaired renal function (creatinine clearance, ≤30 mL/min) in SUMMIT and CREST suggests that bortezomib provides clinical benefit with manageable toxicities in this high-risk population.[44] Renal impairment did not seem to greatly affect the response rate to bortezomib, toxicity, or the likelihood of patients completing the protocol-specified 8 cycles of treatment. Furthermore, data from a prospective National Cancer Institute pharmacokinetic to pharmacodynamic study of bortezomib in adult cancer patients with impaired renal function indicate that bortezomib clearance is independent of renal function and that bortezomib 0.7 to 1.3 mg/m2 is well tolerated in patients with mild (creatinine clearance, 40-59 mL/min) to severe (creatinine clearance, <20 mL/min) renal impairment.[45]

Multiple myeloma patients with renal failure requiring dialysis have been shown to have a particularly poor prognosis.[42] Bortezomib-containing therapy has demonstrated substantial activity in these patients. Results from a recently reported retrospective analysis of 24 MM patients with advanced renal failure requiring dialysis support showed a 75% response rate, including 30% with CR or near CR, with bortezomib-based therapy. Among patients for whom data were available, the median duration of response was more than 12.5 months.[46] Furthermore, renal impairment was reversed in 4 patients after therapy, eliminating the need for dialysis. One patient had a rapid response to treatment and was spared from imminent dialysis, and 3 other patients no longer required dialysis after achieving a CR (2 patients) or a minimal response (1 patient).[46] Although data were limited by the nature of the analysis, the incidence and severity of adverse events in these poor-prognosis patients seemed similar to those reported in APEX, SUMMIT, and CREST, and duration of treatment also seemed comparable.[46] These results suggest that bortezomib-based therapy is active and well tolerated in patients with severe renal impairment.

Advanced age and risk factors such as increased β2-microglobulin levels, low serum albumin levels, abnormal cytogenetics including chromosome 13 deletion, and being refractory to prior treatment are associated with poorer prognosis in MM[3] and may limit treatment options. In a subanalysis of the APEX trial, the efficacy and safety of bortezomib versus dexamethasone were assessed in patients 65 years or older and in high-risk patients, defined as patients with <1 line of prior therapy, patients with International Staging System stage II/III disease (reflecting elevated β2-microglobulin levels and/or low serum albumin levels), or patients refractory to prior treatment. As in the overall population, in these elderly and high-risk patients, bortezomib provided significantly higher response rates and longer time to progression compared with dexamethasone, and grade 3 and 4 adverse events were more common with bortezomib than with dexamethasone.[47] Analysis of the results of the SUMMIT trial for factors predictive of outcome with bortezomib demonstrated that response rate was not associated with the serum β2-microglobulin level or the number or type of previous therapies. By multivariate analysis, only age ≥ 65 years and bone-marrow plasma-cell infiltration < 50% were predictive of a lower response rate and longer time to response[10,48]; however age, serum β2-microglobulin level, and the number or type of previous therapies did not affect time to disease progression, duration of response, or overall survival.[48] Bortezomib also seems to overcome the adverse effects of chromosome 13 deletion on survival and response in the SUMMIT and APEX trials.[49]

Finally, results from a recent study in MM patients with extramedullary involvement at the time of relapse indicate that bortezomib may be active against soft tissue plasmacytomas, whereas other agents, such as thalidomide, are not effective.[50]

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