Sequential Heart and Autologous Stem Cell Transplantation for AL Amyloidosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3092-3092
Author(s):  
Martha Lacy ◽  
Angela Dispenzieri ◽  
Suzanne R. Hayman ◽  
Shaji Kumar ◽  
Robert Kyle ◽  
...  

Abstract Background: Patients with AL and congestive heart failure have a median survival of less than one year. Methods: Between 1994 and 2005, 11 patients underwent sequential heart transplant followed by autologous peripheral blood stem cell transplant (SCT) for treatment of AL. Patients had heart dominant AL with minimal/no other organ impairment and no evidence of multiple myeloma. Results: Patients ranged in age from 35 to 63 years (median 54). All had biopsy proven amyloidosis and monoclonal protein detectable in serum (73%) or urine (100%). Free light chain assay was available prior to SCT in 6 and was abnormal in all. All patients presented with NYHA Class III or IV heart failure. All but two patients had no other organ involved at the time of heart transplant. One patient had his heart transplant at another facility and had renal involvement at the time of heart transplant. One patient had peripheral nerve involvement documented prior to heart transplant. Five patients had progression of amyloid to involve other organs by the time of SCT. These included: renal (6), peripheral nerve (2), macroglossia (3), gastrointestinal (2). The median time from diagnosis to heart transplant was 3 months (range 1 to 5). The median time from heart transplant to SCT was 8 months, (range 3 to 24). Conditioning chemotherapy consisted of melphalan 200 mg /m2 (6 patients) or melphalan 140 mg/m2 (5 patients). Two patients died of complications before day +100, (TRM of 18%). Hematologic remissions were seen in 8 and organ responses in 3. Five were unable to be evaluated for organ response due to the heart transplant. Three died from progressive amyloidosis at 66, 56.7, and 55 months following SCT. The median survival is 56.7 months from SCT. Six are alive with a median follow-up of 24 months, range 9 to 90 months. Among the 6 surviving patients, one patient relapsed and one patient has failed to improve, but 4 patients are in continued remission. One patient developed secondary myelodysplastic syndrome. Conclusions: Heart transplant followed by SCT is feasible and offers durable remissions for carefully selected patients with cardiac AL. Figure Figure

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 46-47
Author(s):  
Iqraa Ansar ◽  
Karun Neupane ◽  
Hamid Ehsan ◽  
Muhammad Yasir Anwar ◽  
Hassaan Imtiaz ◽  
...  

Background: Amyloidosis is characterized by the deposition of misfolded lambda or kappa light chain (AL) proteins in tissue. It commonly affects the heart, which correlates with poor prognosis. Disease-modifying therapies aim to suppress the production of abnormal light chains. Daratumumab (Dara) use is associated with a reduction in light chain protein production. Dara is a human anti-CD38 monoclonal antibody approved for the treatment of newly diagnosed and Relapsed & Refractory Multiple Myeloma. AL amyloidosis plasma cells express CD38, and therefore, Dara is an attractive alternative in this setting. This review aims to assess the efficacy and safety of daratumumab in pre-treated AL amyloidosis patients. Methods: We conducted a comprehensive literature search in PubMed, Embase, Medline using MeSH terms and keywords "AL amyloidosis," "daratumumab", and "darzalex" to incorporate the studies published up to July 2020. We included studies assessing the efficacy and safety of daratumumab alone or in combination with other therapies in pretreated AL amyloidosis. After excluding duplicates, non-relevant, and review articles, we selected four prospective and twelve retrospective studies. RESULTS: In our review, data on 482 patients were included. The ages ranged from 35-88 years. The median number of prior therapies was 3 (ranges:2-6), and the most common therapy was bortezomib in 90% of patients followed by immunomodulators in 55% and stem cell transplant in 35%. A total of 260 (54%) patients received Dara monotherapy, 126 (26%) received Dara plus Dexamethasone (d), and 96 (20%) patients received other Dara containing two or three-drug regimens. The time from the diagnosis to the start of Dara therapy varied from 1 to 137 months. 71 % of patients had cardiac, and 62 % had renal involvement. There was a greater than 30 % reduction of N-terminal pro-brain natriuretic peptide (NT-proBNP) in cardiac patients responsive to therapy. 1. Daratumumab monotherapy: Dara monotherapy achieved an overall response rate (ORR) of 76% (191/249), complete response (CR) of 30% (69/224), very good partial response (VGPR) of 41% (79/192) and partial response (PR) of 14% (19/140). The overall survival (OS) ranges from 59-100% at 10-12 months were noted. Table 1. 2. Daratumumab+ Dexamethasone: Dara plus d achieved ORR of 81% (86/106), CR of 51% (53/102), VGPR of 29% (18/62), PR of 15% (15/102), and OS of 87% at 24 months. Table 1. 3. Daratumumab with combination regimens: The use of Dara based combination regimens of Dara+pomalidomide (P)+d (36% of patients), Dara+lenalidomide (R)+d (32%) and Dara+bortezomib (V)+d (18%), reported by Abeykoon et al., showed an ORR of 88% (14/16), CR of 19 % (3/16), VGPR of 63% (10/16), PR of 6 %(1/16), OS of 89 % at 10 months and progression-free survival (PFS) of 83% at 10 months. Godara et al. reported an ORR of 100% (9/9) using a combination of Dara and birtamimab. The combination of D+cyclophosphamide (c)+V+d reported by Palladini et al. achieved an ORR of 96 % (27/28), CR of 36 % (11/28), VGPR of 29 % (8/28) and PR of 14 % (4/28).Table 1. The most reported adverse event was infusion-related reactions; grade 3-4 adverse were less than 10 % and mostly related to the heart (heart failure & atrial fibrillation). The most-reported hematological adverse effects were anemia, thrombocytopenia, neutropenia, infections, and sepsis. The most common non-hematological adverse events were heart failure, bronchitis, pneumonia, fatigue, nausea, and diarrhea. Table 2. Conclusion: Dara therapy is associated with promising efficacy with a response rate of more than 70% when used alone and more than 80% when used in combination. These regimens are well tolerated in advanced cardiac disease patients with a tolerable risk of volume overload and infusion-related complications. Additional multicenter randomized, double-blind clinical trials are needed to confirm these results. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5906-5906
Author(s):  
Robert Meehan ◽  
David Seldin ◽  
John Mark Sloan ◽  
Karen Quillen ◽  
Dina Brauneis ◽  
...  

Abstract Background: Treatment of AL amyloidosis with high dose intravenous melphalan followed by autologous stem cell transplant (HDM/SCT) is effective in inducing hematologic and clinical remissions associated with prolonged survival. The major toxicities are myelosuppression and GI side effects. Studies have shown that ~75% of melphalan in the blood is bound to plasma proteins, with ~25% free. We hypothesized that AL patients with severe nephrotic syndrome and profound hypoalbuminemia might have a higher fraction of free melphalan, a higher effective dose, and greater toxicity of treatment. Methods: Patients with AL amyloidosis and severe hypoalbuminemia, defined as serum albumin level of < 2 g/dL, treated from 2011 to 2013, were studied retrospectively. The stem cell transplant database was queried for dose of HDM, treatment-related complications, and days of neutrophil and platelet engraftment after SCT. Results: Of 71 patients with AL amyloidosis who underwent HDM/SCT between Jan 2011 and Dec 2013, 12 patients had severe hypoalbuminemia. Of these, 5 received full HDM at 200 mg/m2 and 7 received modified HDM at 140 mg/m2. All patients received GCSF mobilized peripheral blood stem cells following HDM, with a median stem cell dose of CD34+ cells 8.1 x 106/kg (range, 4.0 to 12.2). The median time to engraftment of neutrophils was 11 days, and not statistically different based upon melphalan dose. The median time to platelet engraftment was 13 days, and also did not differ significantly by dose. These times were similar to controls without severe hypoalbuminemia. Grade 4 toxicities were observed in 2 of 7 patients with modified HDM/SCT and 1 of 5 patients with full HDM/SCT. Conclusions: These data suggest that patients with severe hypoalbuminemia do not have more prolonged myelosuppression or increased non-hematologic toxicities compared to other patients. In this retrospective study, we did not measure free melphalan concentrations in the blood. However, these data suggest that patients with severe hypoalbuminemia do not require adjustment of melphalan dosing. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Vol 143 (4) ◽  
pp. 365-372
Author(s):  
Paolo Milani ◽  
Giovanni Palladini

The vast majority of patients with light-chain (AL) amyloidosis are not eligible for stem cell transplant and are treated with conventional chemotherapy. Conventional regimens are based on various combinations of dexamethasone, alkylating agents, proteasome inhibitors, and immunomodulatory drugs. The choice of these regimens requires a careful risk stratification, based on the extent of amyloid organ involvement, comorbidities, and the characteristics of the amyloidogenic plasma cell clone. Most patients are treated upfront with bortezomib and dexamethasone combined with cyclophosphamide or melphalan. Cyclophosphamide does not compromise stem cell mobilization and harvest and is more manageable in renal failure. Melphalan can overcome the effect of t(11;14), which is associated with lower response rates and shorter survival in subjects treated with bortezomib and dexamethasone, or in combination with cyclophosphamide. Lenalidomide and pomalidomide are the mainstay of rescue treatment. They are effective in patients exposed to bortezomib, dexamethasone, and alkylators, but deep hematologic responses are rare. Ixazomib, alone or in combination with lenalidomide, increases the rate of complete responses in relapsed/refractory patients. Conventional chemotherapy regimens will represent the backbone for future combinations, particularly with anti-plasma-cell immunotherapy, that will further improve response rates and outcomes.


2020 ◽  
Vol 4 (17) ◽  
pp. 4175-4179
Author(s):  
Marco Basset ◽  
Paolo Milani ◽  
Mario Nuvolone ◽  
Francesca Benigna ◽  
Lara Rodigari ◽  
...  

Abstract 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.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4917-4917
Author(s):  
A. Keith Stewart ◽  
Young Trieu ◽  
Suzanne Trudel ◽  
Greg Pond ◽  
Joseph Mikhael ◽  
...  

Abstract Alkylating agents remain among the most potent therapies available for treatment of Multiple Myeloma (MM). Their use prior to, or following, autologous stem cell transplant (ASCT) is, however, compromised by concerns about stem cell quality and by myelosuppression limiting effective dose delivered. To address this concern we have studied a combination of cyclophosphamide 500 mg p.o. once weekly and prednisone 100 mg p.o. on alternate days in 66 patients requiring salvage therapy post-ASCT. Dose reductions were allowed for toxicity beginning at cycle 2. On an intent to treat basis, 66 patients received this regimen, however, 7 of these patients were not fully evaluable for response due to non-secretory disease. Of the 59 patients evaluable for response, the median time from transplant to treatment was 26.4 months (range, 6.0 to 66.6). The median time from post-transplant relapse to start of cyclophosphamide and prednisone (C/P) therapy was 1.4 months. The median number of therapies from time of diagnosis to C/P initiation was 2 (range, 1.0 to 5.0). At the date of analysis, treatment with C/P is ongoing in 12 (20.3%) patients, with a median duration of 3.6 months (range, 1.9 to 11.6). The 47 patients who have completed C/P therapy were treated for a median time of 5.5 months (range, 0.5 to 21.7). The reason for discontinuation among these 47 patients included disease progression (42.6% of patients discontinued), plateau disease (21.3%), receiving a second transplant (17.0%), toxicity (10.6%), or switched to another regimen (8.5%). A partial response (&gt;50% protein reduction) was obtained in 37.3% of patients, 18.6% attained minimal response (25–50% protein reduction), 33.8% patients stable disease, while 10.2% patients had progressed on treatment. The estimated median (95% CI) months of progression-free survival after start of C/P treatment is 14.9 (8.7, 21.7). Twenty-three (38.9%) of patients have relapsed after C/P treatment, a median (range) of 8.7 (0.5–65.7) months after start of C/P treatment. At 6 months 74.3% (95% C.I. 61.9% – 89.1%) of patients were progression-free with 28% (95% CI: 16.1–49.2%) progression free at two years. At time of analysis, 44 (74.6%) patients are still alive, with a median follow up of 10.6 months (range, 1.2 to 65.7) since the start of C/P therapy. Fifteen patients have died at a median 13.0 months (range, 1.4 to 61.7) since the time of C/P initiation. The median overall survival (95% C.I.) is estimated to be 35.9 months (24.2, NA). These results demonstrate that the combination of oral cyclophosphamide and prednisone is an effective (56% MR or PR), very well tolerated (10% discontinued due to toxicity) and convenient treatment as salvage MM therapy post-ASCT. The relative lack of myelosuppression allows for re-collection of stem cells and salvage transplant while retaining other active second line agents for later relapse. This regimen thus compares favorably with recent salvage therapeutics introduced in MM and is now being studied in combination with these newer active agents and in induction therapy.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2318-2318
Author(s):  
Karen Quillen ◽  
David C. Seldin ◽  
Kathleen T. Finn ◽  
Vaishali Sanchorawala

Abstract Abstract 2318 Poster Board II-295 High-dose melphalan and autologous stem cell transplant (HDM/SCT) can induce complete hematologic responses (CR), defined as disappearance of the underlying monoclonal gammopathy from serum and urine by immunofixation electrophoresis, and of the clonal plasma cell dyscrasia by bone marrow immunohistochemistry, and extend survival in patients with AL amyloidosis. HDM/SCT results in a CR in 40% of patients, and leads to clinical improvements in organ function in >70% of those who achieve a CR. However, hematologic and clinical relapses occur in ∼8% of patients who initially achieve a CR. Tandem cycles of HDM/SCT, which are typically performed within 12 months of each other, have been shown to achieve a higher ultimate CR rate of >60%. Among patients who do not achieve a CR following a single cycle of HDM/SCT, 30% nonetheless experience improvement in organ function. However, in this latter group, clinical improvement is not durable. We designed a study to explore the feasibility, and efficacy, of a second cycle of HDM/SCT in patients who relapse after initially responding to a first cycle of HDM/SCT. Results: Eleven patients, median age 55 (range 39-62), M:F 7:4, who had achieved hematologic and clinical responses after an initial cycle of HDM/SCT, were treated with a second cycle of HDM/SCT when a hematologic and/or clinical relapse occurred after a median time interval of 34 months (range 12-63). Five patients underwent a second course of G-CSF mobilization and a mean of 5.1 million (range 3.4-7.6 million) CD34 cells/kg was collected in a median of 2 days; the other patients had cells saved from the first mobilization. Six patients received 200 mg/m2 HDM; 5 patients received modified high-dose HDM at 140 mg/m2. Engraftment occurred at a median of 10 days for neutrophils, and 12 days for platelets (two days without platelet transfusion support); this engraftment timing is similar to that following the initial transplants (10 days for neutrophils, 13 days for platelets). There was no treatment-related mortality, but toxicity was moderate; almost all patients (except one) experienced grade III/IV non-hematologic toxicities. Of the 11 patients, 3 achieved hematologic CR at one year; these patients are alive and in continuous remission at 2-6 yr after the second transplant, including one patient who received a subsequent renal transplant. Three patients died of progressive disease at 1-2 years after the second transplant. Five patients are alive at 1-3 years post second transplant, in partial remission. Conclusion: 27% (3/11) of patients with AL amyloidosis who experience a hematologic or clinical relapse after responding to initial HDM/SCT can achieve a hematologic CR with a second course of HDM/SCT. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2400-2400
Author(s):  
Simrit Parmar ◽  
Mubeen Khan ◽  
Gabriela Rondon ◽  
Nina Shah ◽  
Qaiser Bashir ◽  
...  

Abstract Abstract 2400 Background: Approximately 10% of patients with multiple myeloma (MM) have clinically overt primary systemic light-chain (AL) amyloidosis, and about 30% have concurrent occult AL amyloidosis. The impact of concurrent AL amyloidosis on the prognosis of myeloma is not well known. High-dose melphalan followed by autologous hematopoietic stem cell transplant (auto HCT) has shown significant activity in both MM and AL amyloidosis. Methods: We performed a retrospective analysis of patients who had concurrent MM and AL amyloidosis and underwent auto HSCT with high dose Melphalan at MDACC between 01/1998 to 05/2010. We identified 41 patients with concurrent MM and AL amyloidosis. Patient characteristics are summarized in Table 1. Twenty -six patients had occult AL amyloid, while 15 had clinically overt disease. Results: Median age at auto HSCT was 56 years (39-77), 58.5% being male with median follow up of 58.7 months from the time of diagnosis and 42.5 months from auto HCT. The median time from diagnosis to auto HCT was 8.9 mos (2.7-102.4 mos). 39% had Salmon Durie Stage III disease and 36.6% had more than one involved site at the time of transplant.Cytogenetic abnormalities were detected in 24.4% of patients. Post transplant hematologic responses were as follows: ≥CR=10 (24%), ≥VGPR=16 (39%), >PR=33 (80.5%), ≥stable disease= 40 (97.6%). Among the patients with overt organ involvement, one had early death. Of the 15 evaluable patients, organ responses were scored using the published consensus guidelines for amyloidosis and were as follows: PR=5 (33.3%), ≥SD=7 (46.7%). No correlation was seen between organ response and hematologic response. The 100-day treatment related mortality (TRM) was 0 and 1-year TRM of 2.4% which is comparable to patients transplanted for MM alone at our center. The median progression-free (PFS) and overall survival (OS) from auto HCT were 33.8 and 58.3 months, respectively.The median PFS and OS from diagnosis were 49.8 and 96 mos, respectively. In multivariate analysis, creatinine ≥ 2mg/dl was associated with a shorter PFS (p=0.043) and hemoglobin <10g/dl showed a trend towards a shorter PFS (p=0.093). None of these variables (Hb <10g/dl, Age>60yrs, Creatinine≥2mg/dl, B2M >3.5mg/l, BM plasma cells>30%) emerged as significant predictors of OS. There was no significant difference in outcome between patients with occult or symptomatic AL amyloidosis for OS (p=0.24) or PFS (P=0.9) Conclusion: In this analysis the outcome of patients with concurrent MM and AL amyloidosis was comparable to patients with MM alone. We believe these patients are acceptable candidates for auto HCT. Disclosures: Shah: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Research Funding; Novartis: Research Funding. Weber: novartis-unpaid consultant: Consultancy; Merck- unpaid consultant: Consultancy; celgene- none for at least 2 years: Honoraria; millenium-none for 2 years: Honoraria; celgene, Millenium, Merck: Research Funding. Orlowski: Celgene: Consultancy, Research Funding; Millennium Pharmaceuticals, Inc.: Consultancy, Research Funding.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5118-5118
Author(s):  
Tareq Braik ◽  
Dayra Avila ◽  
Shivi Jain ◽  
Manila Gaddh ◽  
Barabara Yim ◽  
...  

Abstract Abstract 5118 Introduction: Since the mid 1990s, high dose chemotherapy with hematopoietic stem cell rescue has been considered the standard of care for front-line treatment in younger patients with multiple myeloma. This standard of care has been based on randomized controlled trials that compared autologus stem cell transplant (ASCT) with conventional chemotherapy. During the past decade, novel agents (NA), thalidomide, bortezomib and lenalinomide, have replaced conventional chemotherapy in the treatment of myeloma. These agents, used frontline, have shown promise in improving the outcome of myeloma patients without increasing toxicity. There are no studies to date comparing NA therapy to ASCT to determine whether there is a survival difference or whether NA therapy may reduce the need for transplantation. Many of our patients have no health insurance coverage and transplant is not a therapeutic option for them. We have attempted to compare the outcome of such patients receiving NA therapy with those in the literature who received conventional chemotherapy followed by ASCT. Methods: Ninety nine patients with multiple myeloma were treated at John H Stroger Hospital of Cook County between 2001 and 2011. All patients received novel agents (thalidomide, bortezomib and lenalinomide) as part of their therapy. Only 18/99 (18.2%) went for high-dose chemotherapy with ASCT and the remaining 81/99 (81.8%) received novel therapy without ASCT. We compared the outcome of patients who received novel therapy alone to a historical control group from the literature who received ASCT with conventional therapy (N Engl J Med 2003;348:1875–83). Overall survival was determined by Kaplan-Meier estimates. Results: We evaluated 99 consecutive myeloma patients (38% males and 61% female) of which 65% were African Americans, 19% Hispanics and 7% whites. All 3 stages (international staging system) of myeloma were equally represented. The median age at diagnosis was 60 years (40–85yr). Median follow up was 48 months (12–120). During the ten year follow up period, 60 patients (60.4%) have died. Twenty four out of 99 patients (24.2%) received only one line of therapy. 75 patients received more than one line of therapy. 75% received thalidomide-based therapy, 13% received bortezomib-based therapy and 12% received lenalinomide-based therapy. The median survival of patients who received novel therapy without ASCT (n=81) was 60 months, which is higher than the median survival of the historical controls who received ASCT reported by Child et al, N Engl J Med 2003;348:1875–83, (median survival = 54.1 months), the difference was statistically significant (P=0.0329). There was no statistically significant difference between the two groups by sex (p=0.927) and race (p=0.421). The 5-year survival of patients who received novel therapy without ASCT (n=81) was 48.2%. For those who were younger than 65 years (n=54), the median survival was 72 months and the 5-year survival was 58.1% in comparison to those who were 65 years and older (n=27), the median survival was 46 months and the 5-year survival was 29.2% (P=0.029). Conclusion: Novel agents are effective frontline therapy for multiple myeloma, especially in patients younger than 65. Our cohort had remarkable results in comparison to a historical population of patients who had ASCT with conventional chemotherapy. Since there is no curative therapy to date, a prospective randomized trial comparing NA with ASCT will be essential to clarify the role of ASCT in the era of novel therapy. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1858-1858 ◽  
Author(s):  
Rahma Warsame ◽  
Soo-Mee Bang ◽  
Shaji K. Kumar ◽  
Martha Q Lacy ◽  
Francis K Buadi ◽  
...  

Abstract Abstract 1858 Systemic light chain amyloidosis (AL amyloidosis) is a condition where clonal plasma cells produce misfolded insoluble immunoglobulin light chains that deposit in various organs causing progressive organ dysfunction. Chemotherapy and autologous stem cell transplant (ASCT) when eligible is the standard treatment options for patients with AL amyloidosis. There are several studies who report long term outcomes of patient post ASCT. However, there is a paucity of literature describing the outcomes of patients who have received ASCT but have relapsed. We performed a retrospective study to assess the outcomes and treatment regimens employed following relapse after ASCT. Between 1996 and 2009, 410 patients received ASCT at the Mayo Clinic as first line therapy. Of those 410 patients 42 patients died within 3 months of transplant, 64 patients died without documented relapse, 158 patients were alive without documented progression, and 146 patients had documented progression. Those 146 patients are the subject of our study. The median time to hematologic relapse was 2 years (range: 0.2–15.5 years). At relapse, 59 patients were treated with IMiD based therapy, 36 with alkylator based therapy, 24 with bortezomib, 15 with steroids, and 5 with second ASCT. The respective hematologic response rates were 58%, 33%, 50%, 53%, and 60%. The remaining six patients were not evaluable for response for one other following reasons: organ transplants; no further therapy; inevaluable disease. With a median post relapse follow up of 3.6 years, the median overall survival (OS) from the first post ASCT relapse was 4.6 years. The median post transplant follow up was 6.1 years, the median OS for these patients was 7.3 years from the time of transplant. These data provide novel information about outcomes after SCT relapse, which should be useful not only for patients and doctors but also for investigators designing studies for salvage therapies post-transplant. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4548-4548
Author(s):  
Catherine Garnett ◽  
Chrissy Giles ◽  
Maialen Lasa ◽  
Osman Ahmed ◽  
Marco Bua ◽  
...  

Abstract Abstract 4548 High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is currently standard treatment for younger patients with multiple myeloma (MM). In the face of almost inevitable disease relapse, there is growing evidence for second ASCT as salvage therapy in certain patient groups. However, few published data exist regarding efficacy and safety of third ASCT in relapsed disease. We retrospectively analysed the results of eight patients treated at a single UK institution who each received three separate autologous stem cell transplants for relapsed MM between May 1997 and April 2012. There were four men and four women. Median age at diagnosis was 48 years (range, 25–64 years). Paraprotein isotype was IgA in two patients and IgG in the remaining six patients. At the time of 1st transplant, seven patients were in partial response (PR) and one in complete response (CR). Conditioning melphalan dose was 200mg/m2 in all but two patients who received 140mg/m2. Three patients entered CR following 1st transplant and four patients showed PR. Median time to disease progression was 31 months (range, 11.8–52.9 months). Prior to 2nd transplant, five patients achieved very good partial response (VGPR) and three PR with induction chemotherapy. Melphalan dose was 200mg/m2 in five patients and 140mg/m2 in the remaining three. Median time to disease progression was 22.3 months (range, 10.1– 39.6 months). At the time of 3rd transplant, two patients had achieved VGPR following induction chemotherapy, one showed PR, two stable disease (SD) and three evidence of disease progression. For the 3rd transplant, melphalan dose was reduced in most cases. Median follow up post 3rd transplant was 8.3 months (range 1.1–29.3 months). One patient died of overwhelming sepsis within one month of transplantation (treatment related mortality). At the time of analysis, five patients had relapsed following 3rd ASCT, with median time to disease progression of 10.4 months (range, 2.7–23.7 months). Three of these patients died at 3.5, 17.6 and 27.1 months post 3rd transplant. The remaining two patients are alive with no evidence of disease relapse (progression free survival (PFS) time of 3.3 and 1.3 months). Overall survival (OS) for the group from diagnosis is 62% at 10 years with a median OS from diagnosis of 149 months (range 68.5 – 189.2 months) (Figure 1). Median OS for the group from 3rd transplant is 17.6 months (range, 1.1–29.3 months) (Figure 2). Median PFS is 10.4 months (range 1.1–23.7 months). These results demonstrate that third ASCT is a possible treatment strategy for patients with relapsed MM and may prolong patient survival. Figure 1: Overall survival from diagnosis for patients receiving 3rd autologous stem cell transplantation for relapsed multiple myeloma Figure 1:. Overall survival from diagnosis for patients receiving 3rd autologous stem cell transplantation for relapsed multiple myeloma Figure 2: Overall survival from time of 3rd autologous stem cell transplant Figure 2:. Overall survival from time of 3rd autologous stem cell transplant Disclosures: No relevant conflicts of interest to declare.


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