Amyloidosis relapsing after autologous stem cell transplantation treated with bortezomib: normalization of detectable serum-free light chains and reversal of tissue damage with improved suitability for transplant.
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ABSTRACT:
SUBMITTER: Brunvand MW
PROVIDER: S-EPMC2833087 | biostudies-literature | 2010 Mar
REPOSITORIES: biostudies-literature
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Amyloidosis relapsing after autologous stem cell transplantation treated with bortezomib: normalization of detectable serum-free light chains and reversal of tissue damage with improved suitability for transplant.
Brunvand Mark W MW Bitter Mitchell M
Haematologica 20091110 3
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Project description:Autologous stem cell transplant (ASCT) is highly effective in selected patients with light chain (AL) amyloidosis. Bortezomib, preceding or following ASCT, improves responses. Satisfactory responses, including at least a partial response, very good partial response (VGPR) with organ response, or complete response, can be observed after induction therapy alone. We report 139 patients treated upfront with cyclophosphamide/bortezomib/dexamethasone (CyBorD), followed by ASCT only if response was unsatisfactory. Only 1 treatment-related death was observed. After CyBorD, hematologic response (HR) rate was 68% (VGPR or better, 51%), with 45% satisfactory responses. Transplant was performed in 55 (40%) subjects and resulted in an 80% HR rate (65% ≥ VGPR). Five-year survival was 86% and 84% in patients treated with ASCT or CyBorD alone, respectively (P = .438). Also, 6- and 12- month landmark analyses did not show differences in survival. Duration of response was not different in the 2 groups (60 vs 49 months; P = .670). Twenty-one (15%) patients with an unsatisfactory response to CyBorD could not undergo ASCT because of ineligibility or refusal; instead, they received rescue chemotherapy, with HR in 38% of cases and 51% 5-year survival. This sequential response-driven approach, offering ASCT to patients who do not attain satisfactory response to upfront CyBorD, is very safe and effective in AL amyloidosis.
| S-EPMC7479942 | biostudies-literature
Project description:BackgroundHistorically, kidney transplantation has been considered inappropriate for most patients with AL amyloidosis-associated kidney failure because of concerns about recurrent disease in the allograft and poor long-term survival. With improvements in rates and durability of hematologic responses and survival that have accompanied treatment advances, a greater proportion of patients with AL amyloidosis may be suitable for kidney transplantation. However, there are no widely accepted criteria for kidney transplant eligibility for this patient population.MethodsWe administered surveys electronically to transplant nephrologists and amyloidosis experts at a geographically diverse set of academic medical centers in the United States. Questions were designed to elucidate views about suitability and timing of kidney transplantation for patients with AL amyloidosis-associated kidney failure.ResultsThe survey was completed by 20 (65%) of invited amyloidosis experts and 20 (29%) of invited transplant physicians. Respondents indicated that, for patients with AL amyloidosis, most transplant nephrologists have limited experience with both determining eligibility for and providing care after kidney transplantation. Most transplant nephrologists and amyloidosis experts viewed anticipated patient survival as the most important determinant of suitability for kidney transplantation. Compared with transplant program respondents, amyloidosis program respondents reported a higher degree of confidence in determining suitability for kidney transplantation, were comfortable proceeding with kidney transplantation earlier after patients attained a hematologic response, and were less concerned about extrarenal amyloid involvement as a barrier to kidney transplantation. In both groups, most respondents indicated that there is a lack of consensus between amyloidosis and kidney transplant physicians about criteria for determining suitability for kidney transplantation.ConclusionViews about criteria for kidney transplantation for patients with AL amyloidosis-associated kidney failure differed between amyloidosis and transplant nephrology program respondents, with amyloidosis specialists generally favoring a less-restrictive approach to transplant eligibility. The findings suggest a need for consensus building across specialties.
| S-EPMC8986034 | biostudies-literature
Project description:BackgroundTreatment protocols for light chain (AL) amyloidosis have been derived from myeloma treatment. Bortezomib is a key drug used for the treatment of myeloma and AL amyloidosis. We retrospectively investigated the efficacy and toxicity of bortezomib- based chemotherapy in patients with newly diagnosed AL amyloidosis.MethodsWe reviewed the outcomes of newly diagnosed autologous stem cell transplantation (auto-SCT)-ineligible AL amyloidosis patients who received bortezomib-based chemotherapy at a referral center between 2011 and 2017.ResultsOf 63 patients who received bortezomib-based chemotherapy, 32 were male, and the median age was 66 years (range, 42‒82 yr). The hematologic overall response rate (ORR) was 65.1%, and the chemotherapy regimen with the best hematologic response was VMP (75.7%, 28/37). Sixty patients had significant organ (heart or kidney) involvement; 28.3% of patients (N=17) had major organ responses after chemotherapy. With a median follow- up of 34 months, there was no significant difference in progression-free survival (P=0.49) or overall survival (P =0.67) according to regimen. Most hematologic and non-hematologic problems were manageable.ConclusionVarious chemotherapy combinations based on bortezomib are currently employed in the clinical setting, but no difference was found in terms of efficacy or toxicity.
| S-EPMC8721454 | biostudies-literature
Project description:We retrospectively reviewed all patients (n = 243) receiving bortezomib, lenalidomide, and dexamethasone (VRd) induction followed by autologous stem cell transplantation (ASCT) for multiple myeloma at the Mayo Clinic between January 2010 and April of 2017. Median age was 61 (interquartile range, 55-67) with 62% of patients being male. High-risk cytogenetic abnormalities (HRA) were present in 34% of patients. A total of 166 (68%) patients received some form of maintenance/other therapy post transplant (no maintenance (NM, n = 77), lenalidomide maintenance (LM, n = 108), bortezomib maintenance (BM, n = 39), and other therapy (OT, n = 19)). Overall response rate at day 100 post ASCT was 99% (CR 42%) with CR rate increasing to 62% at time of best response post transplant. Two year and 5 year overall survival rates were 90% and 67%, respectively, with an estimated median overall survival (OS) and progression-free survival (PFS) of 96 and 28 months, respectively. HRA was associated with a worse OS but not PFS (median OS: not reached for standard risk vs 60 months for HRA, P = 0.0006; median PFS: 27 months for standard risk vs 22 months for HRA, P = 0.70). The combination of VRd followed by ASCT is a highly effective regimen producing deep and durable responses in many patients.
| S-EPMC6224498 | biostudies-literature
Project description:Achieving and maintaining a high-quality response is the treatment goal for patients with newly diagnosed multiple myeloma (NDMM). The phase 3 PETHEMA/GEM2012 study, in 458 patients aged ≤65 years with NDMM, is evaluating bortezomib (subcutaneous) + lenalidomide + dexamethasone (VRD) for 6 cycles followed by autologous stem cell transplant (ASCT) conditioned with IV busulfan + melphalan vs melphalan and posttransplant consolidation with 2 cycles of VRD. We present grouped response analysis of induction, transplant, and consolidation. Responses deepened over time; in patients who initiated cycle 6 of induction (n = 426), the rates of a very good partial response or better were 55.6% by cycle 3, 63.8% by cycle 4, 68.3% by cycle 5, and 70.4% after induction. The complete response rate of 33.4% after induction in the intent-to-treat (ITT) population, which was similar in the 92 patients with high-risk cytogenetics (34.8%), also deepened with further treatment (44.1% after ASCT and 50.2% after consolidation). Rates of undetectable minimal residual disease (median 3 × 10-6 sensitivity) in the ITT population also increased from induction (28.8%) to transplant (42.1%) and consolidation (45.2%). The most common grade ≥3 treatment-emergent adverse events during induction were neutropenia (12.9%) and infection (9.2%). Grade ≥2 peripheral neuropathy (grouped term) during induction was 17.0%, with a low frequency of grade 3 (3.7%) and grade 4 (0.2%) events. VRD is an effective and well-tolerated regimen for induction in NDMM with deepening response throughout induction and over the course of treatment. This trial was registered at www.clinicaltrials.gov as #NCT01916252 and EudraCT as #2012-005683-10.
| S-EPMC6888142 | biostudies-literature
Project description:The role of consolidation post autologous stem cell transplant in light chain amyloidosis is not well defined. We retrospectively identified patients who had light chain amyloidosis and underwent autologous stem cell transplant at the Mayo Clinic. Consolidation was defined as any treatment given after the day 100 evaluation post-transplant to maintain or deepen the response. We identified 471 patients, of whom 72 (15%) received consolidation. Patients receiving consolidation had more advanced disease (Mayo 2012 stage ≥II in 67% vs 52%, P = .02), and had lower day 100 response rates (very good partial response or better: 35% vs 84%, P < .001). After consolidation, rates of very good partial response improved from 24% to 28%, and rates of complete response improved from 11% to 40%. Patients with less than very good partial response who received consolidation, had better progression-free survival (median of 22.4 vs 8.8 months, P < .001), and the benefit was greater in those who deepened their response (median of 41 vs 8.8 months, P < .001). In patients with less than very good partial response, there was a trend for better overall survival in patients who responded to consolidation (median of 125.8 vs 74.4 months, P = .07). In patients who achieved very good partial response, or better, at day 100 post autologous stem cell transplant, consolidation did not improve progression-free or overall survival. Consolidation after autologous stem cell transplant for light chain amyloidosis improves progression-free survival for patients who achieve less than very good partial response.
| S-EPMC7377298 | biostudies-literature
Project description:BackgroundAlthough the use of bortezomib alone and in combination with steroids has shown efficacy in AL amyloidosis, its role in combination with high-dose melphalan and autologous stem cell transplantation (HDM/SCT) is unknown. In this study, we evaluated bortezomib in combination with dexamethasone (BD) for induction chemotherapy prior to HDM/SCT.MethodsThis was a single-center, prospective, randomized controlled trial comparing induction therapy consisting of two BD cycles followed by HDM/SCT (BD + HDM/SCT) with HDM/SCT alone in the treatment of patients with newly diagnosed AL amyloidosis. The hematological and organ responses of the patients were assessed every three months post HDM/SCT.ResultsFifty-six patients newly diagnosed with renal (100%), cardiac (57.1%), liver (7.1%), or nervous system (8.9%) AL amyloidosis were enrolled in this study; 28 patients were assigned to each arm. Two patients died within 100 days of HDM/SCT (3.6% treatment-related mortality). The overall hematologic response rates in the BD + HDM/SCT arm and HDM/SCT arm at three, six and twelve months were 78.5% versus 50%, 82.1% versus 53.5% and 85.7% versus 53.5%, respectively. In the BD + HDM/SCT arm, 15 (53.5%) patients achieved a hematologic response after BD and before HDM/SCT. An intention-to-treat analysis revealed a higher rate of complete remission in the BD + HDM/SCT arm at both 12 and 24 months (67.9% and 70%, respectively) than with the HDM/SCT-only therapy (35.7% and 35%, respectively, P = 0.03). After a median follow-up of 28 months, the survival rates at 24 months post-treatment start were 95.0% in the BD + HDM/SCT group and 69.4% in the HDM/SCT alone group (P = 0.03).ConclusionsOur preliminary data suggest that the outcome of treating AL amyloidosis with BD induction and HDM/SCT was superior to the outcome of the HDM/SCT treatment alone.Trial registrationThis trial has been registered at clinicaltrials.gov with the number NCT01998503.
| S-EPMC3895846 | biostudies-literature
Project description:The HOVON 104 studied bortezomib-dexamethasone induction therapy and autologous stem cell transplantation in 50 patients, of whom 35 received an autologous stem cell transplantation (ASCT). We demonstrate a 5-year overall survival (OS) of 73% and progression-free survival (PFS) of 52% for all 50 patients with a median follow-up of 61.3 months. For the 35 transplanted patients, calculated from the date of ASCT, the 5-year OS and PFS were 91% and 68%, respectively. After ASCT, the rate of organ response improved over time but stabilized around 3 years. A complete cardiac response was seen in around 60% of patients and remained stable from 2 years onward. Reaching complete renal response was slower over time and achieved by 61% of the renal-affected patients at 5 years. We confirm the excellent outcomes after ASCT and demonstrate a 60% complete organ response with longer follow-up.
| S-EPMC11327711 | biostudies-literature
Project description:Autologous stem cell transplantation (ASCT) is a standard treatment for eligible multiple myeloma (MM) patients, but many patients will relapse after ASCT and require subsequent therapy. The proteasome inhibitor carfilzomib is approved for relapsed or refractory MM (RRMM). In phase 3 trials, carfilzomib-based regimens (ASPIRE, carfilzomib-lenalidomide-dexamethasone; ENDEAVOR, carfilzomib-dexamethasone) demonstrated superior progression-free survival (PFS) compared with standard therapies for RRMM (ASPIRE: lenalidomide-dexamethasone; ENDEAVOR, bortezomib-dexamethasone). This subgroup analysis of ASPIRE and ENDEAVOR evaluated outcomes according to prior ASCT status. In total, 446 patients in ASPIRE and 538 in ENDEAVOR had prior ASCT. Median PFS was longer for carfilzomib-based regimens vs non-carfilzomib-based regimens for patients with prior ASCT (ASPIRE: 26.3 vs 17.8 months (hazard ratio (HR)=0.68); ENDEAVOR: not estimable vs 10.2 months (HR=0.61)), those with one prior line of therapy that included ASCT (ASPIRE: 29.7 vs 17.8 months (HR=0.70); ENDEAVOR: not estimable vs 11.2 months (HR=0.46)), and those without prior ASCT (ASPIRE: 26.4 vs 16.6 months (HR=0.76); ENDEAVOR: 17.7 vs 8.5 months (HR=0.43)). Overall response rates also favored the carfilzomib-based regimens. No new safety signals were detected. This analysis suggests that carfilzomib-based treatment may lead to improvement in PFS and response rates regardless of prior transplant status. Further evaluation is warranted.
| S-EPMC5729352 | biostudies-literature
Project description:IntroductionAutologous stem cell transplantation (ASCT) following high-dose chemotherapy is applied as salvage therapy in patients with relapsed disease or as first-line consolidation in high-risk DLBCL with chemo-sensitive disease. However, the prognosis of relapsing DLBCL post-ASCT remained poor until the availability of CAR-T cell treatment. To appreciate this development, understanding the outcome of these patients in the pre-CAR-T era is essential.MethodsWe retrospectively analyzed 125 consecutive DLBCL patients who underwent HDCT/ASCT.ResultsAfter a median follow-up of 26 months, OS and PFS were 65% and 55%. Fifty-three patients (42%) had a relapse (32 patients, 60%) or refractory disease (21 patients, 40%) after a median of 3 months post-ASCT. 81% of relapses occurred within the first year post-ASCT with an OS of 19% versus 40% at the last follow-up in patients with later relapses (p=0.0022). Patients with r/r disease after ASCT had inferior OS compared to patients in ongoing remission (23% versus 96%; p<0.0001). Patients relapsing post-ASCT without salvage therapy (n=22) had worse OS than patients with 1-4 subsequent treatment lines (n=31) (OS 0% versus 39%; median OS 3 versus 25 months; p<0.0001). Forty-one (77%) of patients relapsing after ASCT died, 35 of which due to progression.ConclusionsAdditional therapies can extend OS but mostly cannot prevent death in DLBCL relapsing/refractory post-ASCT. This study may serve as a reference to emerging results after CAR-T treatment in this population.
| S-EPMC10171206 | biostudies-literature