Impact of pretransplant therapy in patients with newly diagnosed myeloma undergoing autologous SCT

Kumar, Shaji; Dingli, David; Dispenzieri, Angela; Lacy, Martha Q.; Hayman, Suzanne R.; Buadi, Francis K.; Rajkumar, S. Vincent; Litzow, Mark R.; Gertz, Morie A.

doi:10.1038/bmt.2008.24

Cited by 22 publications

(15 citation statements)

References 32 publications

(45 reference statements)

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“…In addition, there is one small randomized trial [25] and a limited number of small single arm [26] and retrospective studies [27] , [28] that suggest benefit of induction prior to ASCT, but the analysis of which patients derive the most benefit had not been addressed. Finally, patients with multiple myeloma typically receive 3-6 cycles of induction prior to stem cell collection and ASCT, [29] and deeper responses pre-ASCT have consistently yielded deeper responses post ASCT. [30] The use of induction may also reduce ASCT TRM by giving the sickest patients the opportunity to demonstrate their lack of suitability for ASCT during their initial therapy.…”

Section: Discussionmentioning

confidence: 99%

Induction therapy pre‐autologous stem cell transplantation in immunoglobulin light chain amyloidosis: a retrospective evaluation

et al. 2016

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There is no consensus on whether patients with immunoglobulin light chain amyloidosis (AL) should receive induction therapy prior to an autologous stem cell transplant (ASCT). This study investigated the relationships between baseline bone marrow plasmacytosis (BMPC), cardiac staging, and pre-transplant induction in AL patients. All patients who received ASCT for AL within 12 months of diagnosis were included. Patient characteristics and outcomes were abstracted. Univariate and multivariate modeling was performed. Among 415 AL patients, 35% had induction prior to ASCT. Post-ASCT hematologic CR plus VGPR rates were significantly higher in those with baseline BMPC ≤ 10% compared to BMPC >10% (58% versus 40%, P = 0.0013). Significant risk factors for lack of attainment of CR included attenuated dose melphalan conditioning, baseline BMPC > 10%, no induction, and male gender. The 5-year OS for the entire group was 65%. On multivariate analysis, risk factors for inferior OS included no induction therapy, advanced AL amyloid staging, BMPC > 10%, attenuated conditioning melphalan dose, and male gender. Patients with Mayo 2012 stage I-II patients with BMPC ≤ 10%, who comprised 56% of the ASCT population fared exceedingly well regardless of whether or not they received induction therapy with a 5-year OS of 81 to 83%. Induction therapy pre-ASCT may improve outcomes among AL patients due to a rapid reduction of toxic light chains or alternatively by elimination of less fit patients by "testing" their ability to tolerate chemotherapy. Prospective studies will be required to sort out these and other questions. Am. J. Hematol. 91:984-988, 2016. © 2016 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Induction therapy pre‐autologous stem cell transplantation in immunoglobulin light chain amyloidosis: a retrospective evaluation

et al. 2016

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“…In recent times, thalidomide, bortezomib, and lenalidomide have emerged as effective therapies and have been used for induction therapy instead of VAD regimens [24]. These new agents have shown additive or synergistic effects in combination with dexamethasone during in vitro and in vivo studies [25,26], but regimens containing HD would be associated with significant toxicity and treatmentrelated early mortality rates [27].…”

Section: Discussionmentioning

confidence: 99%

Reduced risk of bacterial infection in multiple myeloma patients with VAD regimen without intermittent high-dose dexamethasone

et al. 2010

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Vincristine-adriamycin-dexamethasone (VAD) regimen with intermittent high-dose dexamethasone (HD) has been used as primary chemotherapy for multiple myeloma (MM) patients who are candidates for high-dose therapy or present with renal failure. However, dexamethasone increases the risk of infection in MM patients. We retrospectively evaluated treatment efficacy and infectious events in MM patients undergoing VAD with or without HD. Seventy-seven consecutive patients who received VAD without HD (n = 37) or VAD-HD (n = 40) at our institution were assessed. Characteristics of patients and VAD regimens were retrospectively analyzed to detect correlations with the incidence of infections. During 218 VAD cycles, 48 infectious episodes were documented in 39 patients. Of these, 32 episodes in 26 patients were severe (grade ≥ 3). By analyzing each patient, VAD-HD was associated with risk of all-grade and severe bacterial infection, while International Staging System stage ≥ 2 was independently correlated with severe bacterial infection. Response rates after two cycles were comparable between the 2 VAD regimens. In conclusion, risk of infection is lower in VAD without HD than in VAD-HD, and the clinical response is equivalent. VAD-HD should thus be avoided for MM patients with high risk of infection.

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“…26 Previously, the administration of high-dose therapy was performed whether or not a response to induction therapy occurred, with no compromise in PFS or overall survival. 27 In one study, those patients achieving a complete response after transplantation had significantly improved overall and event-free survival (P Ͻ .01) compared with near-complete responders, who in turn did better than partial responders. 28 These outcomes were independent of age.…”

Section: Discussionmentioning

confidence: 99%

Stem cell transplantation in multiple myeloma: impact of response failure with thalidomide or lenalidomide induction

Gertz

Kumar

Lacy

et al. 2010

Blood

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Autologous stem cell transplantation as a platform for multiple myeloma treatment is the standard of care for patients who can safely withstand the procedure. Before novel agents were introduced, onethird to one-half of patients did not achieve partial response at transplantation. Previous medical literature has shown that in this past era, absence of initial response to induction therapy had no impact on progression-free survival and overall survival after highdose therapy. Lack of response to initial induction did not preclude a good response after stem cell transplantation. With the introduction of novel agentsimmunomodulatory drugs and proteasome inhibitors-response rates with initial therapy are now between 70% and 100%. This retrospective study analyzes progression-free survival and overall survival in patients who do not have a partial response (never responded or progressed during continuous therapy) after induction therapy with a regimen that contains thalidomide or lenalidomide. Unlike patients in reports published previously-before immunomodulatory drugs-patients who do not achieve partial remission have a significantly shorter overall survival from transplantation (73.5 vs 30.4 months) and a shorter progression-free survival (22.1 vs 13.1 months; P < .001). Absence of a response to induction therapy with thalidomide or lenalidomide predicts a poorer outcome after high-dose therapy. (Blood. 2010;115:2348-2353)

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Impact of pretransplant therapy in patients with newly diagnosed myeloma undergoing autologous SCT

Cited by 22 publications

References 32 publications

Induction therapy pre‐autologous stem cell transplantation in immunoglobulin light chain amyloidosis: a retrospective evaluation

Induction therapy pre‐autologous stem cell transplantation in immunoglobulin light chain amyloidosis: a retrospective evaluation

Reduced risk of bacterial infection in multiple myeloma patients with VAD regimen without intermittent high-dose dexamethasone

Stem cell transplantation in multiple myeloma: impact of response failure with thalidomide or lenalidomide induction

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