Factors Influencing Outcomes of Relapse from Front-Line Autologous Stem Cell Transplant (ASCT) over a 14 Year Period: A Single Centre Experience

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3465-3465
Author(s):  
Selina J Chavda ◽  
Paul Michael Maciocia ◽  
Pavlina Mesiri ◽  
Nicholas Counsell ◽  
Jaimal Kothari ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Salvage Therapy ◽  
Cox Regression ◽  
Treatment Strategies ◽  
Autologous Stem Cell Transplant ◽  
Clinical Relapse ◽  
Cell Transplant ◽  
Salvage Regimen ◽  
Patient Counselling ◽  
Equity Ownership

Abstract Background. Chemotherapy followed by ASCT is standard of care in fit transplant-eligible newly diagnosed patients with Multiple Myeloma (MM). Most patients, however, will relapse and require further treatment. With increasing choice of therapies at relapse, we need to understand the determinants of treatment outcomes for these patients, to aid management decisions and patient counselling. Methods. This was a retrospective analysis of sequential patients who relapsed from upfront ASCT carried out between 2000-2014. PFS1 was defined as time from ASCT to 1st progression or death; PFS2, time from ASCT to 2nd progression or death and 2nd PFS, time from start of salvage regimen to 2nd progression or death. Post relapse survival (PRS) was measured from progression date and overall survival (OS) from ASCT date. Disease response, and adverse FISH were assigned according to IMWG. Survival was estimated using Kaplan- Meier curves and correlative analysis by Cox regression models. Results. Of 474 patients undergoing ASCT (2000-2014), 277 relapsed with a median age of 58 years (range 29-70).The M:F ratio was 1.85:1. Isotypes identified were: IgG 57.0%, IgA 22.7%, light chain 15.9%. Median PFS1 from ASCT was 20 months (0.47-128.3). ORR pre-ASCT was 91.3% (sCR/CR 4.4%, VGPR 25.4%) and post ASCT was 95.3% (sCR/CR 14.5%, VGPR 52.2%). At relapse, median age was 60 years (30-73) and 36.5% of patients had ISS stage2-3 disease. For the 277 patients who relapsed, median OS from ASCT was 67 months (CI 57-73) and median PRS was 40 months (35-44). PFS1 had a strong influence on OS, HR 0.97 (95%CI: 0.96-0.97, p<0.001), and PRS HR 0.99 (0.98-0.996, p=0.004). Patients relapsing before 2008 (prior to bortezomib funding) had shorter OS compared to those relapsing thereafter: median 61 vs 69 months, HR 1.38 (1.01-1.87, p=0.04). Depth of response (CR/VGPR) pre and post-ASCT were associated with longer PFS1- HR 0.70 (0.54-0.92, p=0.01), and HR 0.68(0.51-0.89, p=0.005) respectively, but not OS or PRS. 248 patients (89.5%) received systemic salvage therapy at relapse;106 patients (38.3%) experienced biochemical IMWG progression rather than clinical relapse, with median time to treatment of 5 months (2-64). Salvage regimens included: proteasome inhibitors(PIs) (64.5%), immunomodulatory agents (IMiDs, 29.8%, thalidomide-63.5%, lenalidomide-36.5%) and chemotherapy 5.2%; 26.6% of patients entered clinical trials and 13.7% underwent salvage ASCT. ORR was 70.4% (sCR/CR 10.9%, VGPR 31.6%). Median 2nd PFS was 17 months (16-20) and median PFS2 overall was 39 months (35-41). Achieving a deeper response to salvage treatment (CR/VGPR) was associated with a longer 2nd PFS (21 vs 17 months for PR, HR 0.65, 0.46-0.91, p=0.01), with a trend for PRS, HR 0.89(0.59-1.34, p=0.58) and OS, HR 0.77(0.51-1.17, p=0.22). Novel agents induced deeper responses, CR/VGPR with PI regimens 51.3%, with IMiDs 30%, and with chemotherapy 8%. Patients treated with PIs compared to all other systemic treatment regimens had a significantly longer OS of 80 vs 48 months, HR 0.60(0.43-0.85, p= 0.004). Patients entered into clinical trials (66) had deeper responses, ≥VGPR 61% compared to 31% in non-trial patients, and longer PRS, 64 vs 35 months, HR 0.54 (0.36-0.81, p= 0.003) and OS 90 vs 57 months, HR 0.50 (0.33-0.76, p=0.001). Risk factors at relapse influenced outcomes. Higher ISS was associated with shorter PRS, ISS 2/3 27 vs 50 months for ISS1, HR 2.52(1.74-3.66, p<0.0001) and OS, 46 vs 82 months, HR 2.42(1.67-3.50, p<0.0001). Presence of adverse FISH at relapse (54.1% of 133 patients) also predicted shorter PRS (restricted mean survival time 40 vs 72 months, p<0.001) and OS, 59 vs 97 months for standard FISH, HR 0.46 (0.28-0.73, p=0.0011). Adverse FISH at diagnosis (25.5% of 157) also predicted poorer outcomes. Conclusions. This real-world series shows that timing of relapse, period of relapse (pre-2008), ISS Stage, adverse FISH, and response to salvage regimen influence survival after relapse from frontline ASCT. Use of novel regimens, particularly PIs as salvage therapy post ASCT is associated with longer OS. Our data confirm the importance of entering patients into clinical trials. Multivariable linear regression analyses will be presented. Lastly, the inferior outcomes for patients with high-risk features highlights the need to develop different treatment strategies in this patient subgroup. Disclosures Maciocia: Autolus: Equity Ownership, Patents & Royalties: TRBC1 and 2 Targeting for the Diagnosis and Treatment of T-cell Malignancies. Yong:Janssen: Research Funding; Autolus Ltd: Equity Ownership, Patents & Royalties: APRIL based chimeric antigen receptor.

scholarly journals Outcomes of Adult Patients with Relapsed/Refractory Burkitt or Burkitt-like Leukemia/Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5150-5150
Author(s):  
Nicholas J. Short ◽  
Elias J. Jabbour ◽  
Heidi Ko ◽  
Farhad Ravandi ◽  
Deborah A Thomas ◽  
...  
Keyword(s):  
Salvage Therapy ◽  
Research Funding ◽  
Treatment Strategies ◽  
Late Relapse ◽  
Cell Transplant ◽  
Salvage Regimen ◽  
Early Relapse ◽  
Entire Cohort ◽  
Remission Duration ◽  
Frontline Therapy

Abstract Background: Burkitt leukemia/lymphoma is a highly aggressive B-cell neoplasm that is potentially curable with chemoimmunotherapy. While patients (pts) who are refractory to initial therapy or subsequently relapse are considered to have a poor prognosis, few studies have systematically evaluated the outcomes of these pts. Methods: We retrospectively identified 146 adult pts with Burkitt or Burkitt-like leukemia or lymphoma treated at our institution between 1992 and 2013 with frontline hyper-CVAD-based regimens. 12 pts died before initial response assessment and 4 were unevaluable due to inadequate records; these pts were therefore excluded from the analysis. Among the 130 pts evaluable for response, 36 pts (28%) had relapsed (n=33) or refractory (n=3) Burkitt or Burkitt-like leukemia/lymphoma and are the subject of this analysis. Early and late relapse were defined as relapse <6 months and ≥6 months from the time of first remission, respectively. Overall response rate (ORR) defined as the composite of complete remission (CR) and partial remission (PR), relapse-free survival (RFS), and overall survival (OS) were evaluated. Results: The median age of the evaluable population was 51 years (range, 18-76 years). Among the 36 relapsed/refractory pts, initial presentation was leukemia in 29 pts and lymphoma in 7 pts. Initial treatment was hyper-CVAD alone in 11 pts, hyper-CVAD plus rituximab (R-hyper-CVAD) in 24 pts, and hyper-CVAD plus ofatumumab in 1 pt. Among the 33 relapsed pts, 30 had achieved CR to frontline treatment and 3 had only achieved PR. The median time to first relapse was 6.6 months (range 0.7-75.3 months). Twelve pts (36%) and 21 pts (64%) experienced early and late relapse, respectively. Thirty relapsed/refractory pts received at least one salvage regimen, 29 of whom were evaluable for response. The backbone salvage regimens received were hyper-CVAD in 13 pts (43%), ICE in 6 (14%), EPOCH in 2 (7%), MOAD in 2 (7%), and miscellaneous regimens in 7 (23%). Subsequent stem cell transplant (SCT) was performed in 6 pts (allogeneic, n=3; autologous, n=3). The ORR to salvage chemotherapy was 38% (CR, n=8; PR, n=3); 18 pts were refractory. Among the 18 pts with late relapse who received salvage therapy, the ORR was 61%. In contrast, of the 11 pts who were refractory to frontline therapy or had early relapse, none responded to salvage therapy (P<0.001 vs. pts with remission duration ≥6 months). The median OS for the entire cohort (measured from time of relapse or treatment failure) was 2.7 months, with a 1-year OS rate of 10% (Figure 1A). Among responding pts, the median RFS was 3.3 months, with a 1-year RFS rate of 18% (Figure 1B). Only 2 pts were still alive without relapse at last follow-up, one who had undergone salvage autologous SCT and one who had a late relapse 75 months after initial diagnosis and was treated with R-EPOCH without SCT consolidation. Pts who responded to salvage treatment had superior OS compared to those who did not (median OS: 7.5 months vs. 1.5 months, respectively; P<0.001). Pts with late relapse had a median OS of 5.0 months, compared to only 1.4 months for those who were refractory to frontline therapy or experienced early relapse (P<0.001). Conclusions: Pts with relapsed/refractory Burkitt leukemia/lymphoma have very poor outcomes, with an ORR to salvage therapy of 38% and a median OS of only 2.7 months. Pts with a remission duration after frontline therapy of ≥6 months have superior outcomes, although the OS of this group is still poor. Novel treatment strategies are needed for pts with relapsed/refractory disease. Disclosures Jabbour: ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy. Cortes:ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding. Wierda:Abbvie: Research Funding; Acerta: Research Funding; Novartis: Research Funding; Gilead: Research Funding; Genentech: Research Funding. Thompson:Pharmacyclics: Consultancy, Honoraria.

scholarly journals Natural History and Prognostic Factors at First Relapse in Multiple Myeloma

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1759
Author(s):  
Chen Wang ◽  
Cinnie Yentia Soekojo ◽  
Sanjay de Mel ◽  
Melissa Ooi ◽  
Yunxin Chen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Natural History ◽  
Great Majority ◽  
Autologous Stem Cell Transplant ◽  
Clinical Relapse ◽  
Cell Transplant ◽  
Treatment Sequence ◽  
World Picture ◽  
First Relapse ◽  
Relapsed Myeloma

The prognosis of multiple myeloma has considerably improved due to the introduction of novel agents in the upfront setting. However, the great majority of patients ultimately relapse, and choosing a salvage treatment at first relapse remains challenging. The natural history of first relapsed disease in the current era is also not well described. We retrospectively studied 300 patients with first relapsed myeloma seen between 2004 and 2019 from two institutes in Singapore. The median duration from diagnosis to first relapse was 22.7 months (1.1–97.0 months). Most patients received novel agent-based induction therapy, and 41.3% underwent autologous stem cell transplant. A very good partial response (VGPR) or better was achieved in 48.6%. Regarding first relapse, 50.5% were symptomatic and 19.0% received newer agent-containing regimens. Nearly a third of patients (31.7%) had a VGPR or better response. The median progression free and overall survival from first relapse was 12.0 and 44.8 months, respectively. Based on a randomized sample splitting, we first identified non-hyperdiploid karyotype at diagnosis, clinical relapse, and treatment sequence as impacting survival independently from a testing cohort, and we then further demonstrated their significance in a validation cohort. This study provides a real-world picture of first relapsed myeloma and highlights the prognostic importance of the treatment sequence.

A Phase II Study of Velcade (V), Doxil (D) in Combination with Low-Dose Thalidomide (T) as Salvage Therapy for Patients (pts) with Relapsed (rel) or Refractory (ref) Multiple Myeloma (MM) and Waldenstorm Macroglobulinemia (WM): Encouraging Preliminary Results.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2421-2421 ◽  
Author(s):  
Asher Alban Chanan-Khan ◽  
Kena C. Miller ◽  
Philip McCarthy ◽  
Laurie A. DiMiceli ◽  
Jihnee Yu ◽  
...  
Keyword(s):  
Phase Ii ◽  
Salvage Therapy ◽  
Low Dose ◽  
Treatment Options ◽  
Hematologic Malignancies ◽  
Cell Transplant ◽  
Synergistic Activity ◽  
Salvage Regimen ◽  
Highly Active ◽  
Development Of Resistance

Abstract In MM, tumor microenvironment (ME) plays an important role in disease progression, dissemination, and development of resistance to therapy. Pts with rel/ref MM have limited treatment options. Therefore, targeting the ME simultaneously with malignant cells may be an effective way to overcome resistance in pts with rel/ref MM. Orlowski et al recently reported synergistic activity of V+D in patients with hematologic malignancies. A phase II trial initiated at our institute is exploring this approach, targeting the MM cell as well as its ME, using a combination of Velcade (V), Doxil (D) and low-dose thalidomide (T) as salvage therapy for pts with rel/ref MM. Pts with rel/ref disease are eligible for this study. V is given at 1.3mg/m2 (D1,4,15,18) and D at 20mg/m2 (D1,15) every 4 weeks with daily T (200 mg) for 4–6 cycles. SWOG criterion was used to evaluate response. Low-dose coumadin (1–2 mg po qd) was used for prevention of venous thromboembolism (VTE). Eighteen pts (7M, 11F; median age 56, range 44–80 yrs; 16MM, 2 WM) have been enrolled to date. All pts had Stage III disease, median b2M of 4.8 (nl range: 0–2.15) and median prior therapies 2 (range 1–7). Prior therapies included stem cell transplant in (46%), T (54%), adriamycin(A) (70%) and steroids (92%). Thirteen pts have completed at least 1 cyc and are available for toxicity and response evaluation. One pt died of sepsis prior to completing 1 cyc and 1 pt with PR was taken of study for non-compliance after 1 cyc. ORR was 100% (13/13) with 5PR and 8MR. All pts are currently continued on therapy. Toxicity: 2 pts developed Gr. II plantar-palmar erythrodysthesia (PPE) and 1 had Gr. III cellulitis. No VTE was noted. VDT is a highly active salvage regimen in pts with rel/refr MM. Responses were noted despite prior failure of steroids, T or A. It is well tolerated without any significant non-hematologic Gr. III/IV toxicity. VTE does not appear to be a problem. Updated results of this first cohort of pts will be presented at the annual ASH meeting.

Patterns and Timing of Initial Relapse in Patients with Hodgkin’s and Non-Hodgkin’s Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3673-3673 ◽  
Author(s):  
Sughosh Dhakal ◽  
Tithi Biswas ◽  
Sheema Chawla ◽  
Nikhil Uppal ◽  
Christopher Beck ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Early Stage ◽  
Treatment Strategies ◽  
Autologous Stem Cell Transplant ◽  
Hodgkin's Lymphoma ◽  
Cell Transplant ◽  
Local Recurrences ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Aggressive Histology

Abstract Purpose/Objective: To evaluate patterns of recurrence in patients with Hodgkin’s (HL) and non-Hodgkin’s lymphoma (NHL) who subsequently undergo autologous stem cell transplant (ASCT). In this population that has declared itself as high risk, we evaluated time to and sites of relapse relative to initial sites of disease and radiation therapy (RT). This information might enhance understanding of the natural history of these diseases in the setting of modern therapy, influence treatment strategies, and assist in screening decisions. Materials/Method: We analyzed the records of all 281 consecutive patients with refractory or recurrent HL and NHL (indolent and aggressive, as defined at initial diagnosis) who underwent ASCT in our center between 5/92–7/03. Patients were initially diagnosed between 1979–2003 at a median age of 44 years (8–70). 25 patients were unevaluable due to insufficient data, and 68 patients were excluded from analysis because their disease was refractory to initial and salvage therapy. HL patients were segregated according to initial staging (I/II vs. III/IV). Results: Early stage HL patients relapsed at a median of 2.0 years (0.5–10.3) with 87% relapsing in initial disease site(s); 13% (95% CI 3.8–30.1%) relapsed only in new sites. Advanced stage HL patients relapsed at a median of 1.4 years (0.6–10.5) with 96% relapsing in initial site(s); 4% (95% CI 0.1–21.9%) relapsed only in new sites. Indolent histology NHL patients relapsed at a median of 2.1 years (0.5–14.9) with 83% relapsing in initial site(s); 17% (95% CI 7.3–32.8%) relapsed only in new sites. Aggressive histology NHL patients relapsed at a median of 1.0 year (0.3–8.0) with 64% relapsing in initial site(s); 36% (95% CI 26.2–46.2%) relapsed only in new sites. For early stage HD patients, recurrences were predominantly local, and uniformly so in those unirradiated. For all other groups, fewer patients were irradiated than unirradiated and local recurrences predominated regardless of therapy. Conclusions: Almost all patients with HL who relapse and subsequently undergo ASCT initially recur in previous disease sites. Although patients with aggressive histology NHL are more likely to relapse in new sites than patients with indolent NHL, local recurrences predominate in both groups. The median time to recurrence is brief (1–2.1 years). In a population defined by recurrent disease, it is expected that relapses will occur in irradiated sites. Relative protection by RT of local recurrence cannot be determined until all patients, regardless of relapse status, are analyzed. However, these data support an emphasis on local control and suggest that the frequency of screening be most rapid in the early post-therapy years. Comparison of Site(s) of Relapse to Site(s) of Initial Presentation HL NHL Early (n=30) Adv. (n=23) Ind. (n=40) Agg. (n=95) Characteristic % % % % New Site(s) 13 4 18 36 Previous site(s) only 63 61 60 44 Previous site(s) + new site(s) 23 35 23 20 Characteristic n n n n Radiated patients relapsing in previous site(s) 15/19 6/6 5/7 20/34 Unradiated patients relapsing in previous site(s) 11/11 16/17 26/33 42/61

Second Autologous Stem Cell Transplant (ASCT) as Salvage Therapy in Patients with Relapsed Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1217-1217
Author(s):  
Joseph R. Mikhael ◽  
Sahar Zadeh ◽  
A. Keith Stewart ◽  
Christine Chen ◽  
Suzanne Trudel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Salvage Therapy ◽  
Median Overall Survival ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Free Survival ◽  
Free Interval ◽  
Ortho Biotech

Abstract Abstract 1217 Poster Board I-239 Background Single autologous stem cell transplant (ASCT) is considered the standard of care after induction therapy for younger multiple myeloma (MM) patients (pts). However, it is not curative and virtually all patients will ultimately relapse. As more options are available to treat relapsed disease, the role of a second ASCT as salvage therapy is unclear. Method Retrospective review of all MM pts who received a 2nd ASCT as salvage therapy at Princess Margaret Hospital. Results Between February 1997 and July 2009, 79 MM pts received a second ASCT for relapsed MM at our institution. Median age was 60 yrs (range 39-72) at second transplant. 48 pts (61%) were male. Immunoglobulin subtype included IgG (42), IgA (21), light chain (11), nonsecretory (3), IgM(1) and IgD (1). Transplant conditioning regimen for first transplant was high dose melphalan (MEL) 140-200 mg/m2 in 67, busulphan and cyclophosphamide in 1, and combinations of MEL with etoposide (E) or TBI in the rest. 2nd ASCT conditioning consisted of MEL alone in 76, the remaining 3 had MEL with either TBI or E. The median time to relapse after the first transplant was 2.72 years (0.81-8.26), with a median interval between transplants of 3.61 years (1.63-9.59). Response to first transplant in 78 evaluable patients was 13 CR/nCR (17%), 56 PR/VGPR (72%), 9 MR/SD (12%). Nineteen pts received maintenance therapy between transplants. Two transplant-related deaths occurred following 2nd ASCT. In 73 evaluable patients, response to second transplant was 11 CR/nCR (15%), 57 PR (78%), 6 MR/SD (8%). After 2nd ASCT, with median follow up 5.92 years (71 months), median progression-free survival (PFS) was 18.5 months and median overall survival (OS) was 4.4 years. Long term progression-free status based on the progression-free interval after 1st ASCT is summarized Table 1. PFS based on progression free interval after 1st ASCT is outlined in Figure 1. Conclusions 2nd ASCT is a feasible and safe salvage therapy in relapsed MM patients. It is effective in providing a median progression free survival of 18.5 months and median overall survival of 4.4 years (52.8 months) after 2nd ASCT. This is comparable if not better than modern salvage chemotherapies. The longer the disease free interval after 1st ASCT the more effective 2nd ASCT is at extending both progression free survival and overall survival. It is reasonable, therefore, to consider a 2nd ASCT if the time to progression is greater than 2 years after first ASCT. Disclosures Chen: Celgene: Honoraria, Research Funding; Ortho Biotech: Honoraria. Trudel:Celgene: Honoraria, Speakers Bureau; Ortho Biotech: Honoraria. Kukreti:Celgene: Honoraria.

Prognostic significance of t(11;14) expression by FISH in patients with newly diagnosed multiple myeloma in the era of novel therapies.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19525-e19525
Author(s):  
Miguel Gonzalez Velez ◽  
Ricardo Daniel Parrondo ◽  
Tracy Andrews ◽  
Narjust Duma ◽  
Joshua Ryan Richter ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Novel Therapies ◽  
Newly Diagnosed ◽  
Seer Data ◽  
Worse Prognosis

e19525 Background: Rearrangements of the immunoglobulin heavy chain (IGH) on chromosome 14 are identified by FISH in about 15-20% of patients (pts) with newly diagnosed multiple myeloma (MM). Historically there is variation on the significance on prognosis of these rearrangements: typically, t(4;14), t(14;16) and t(14;20) have high risk (HR), and t(11;14) have standard risk (SR). A recent study (Kaufman et al, Leukemia. 2016 30:633-9) suggests that t(11;14) may confer a worse prognosis We report the prognostic significance of t(11;14) in a single-institution MM cohort. Methods: 87 pts with t(11;14) by CD 138 selected FISH at diagnosis were identified, pts without symptomatic MM were excluded. Cox regression was used for statistical analysis. Progression free survival (PFS), and overall survivals (OS) from diagnosis and post autologous stem cell transplant (ASCT) were analyzed by Kaplan-Meier. Results: Median age at diagnosis was 62 years, 45 pts (52%) were male, and 24 pts (27%) had ISS 3. All pts received either a proteasome inhibitor or an immunomodulatory agent, and 42 (48%) received triplet treatment as induction. Sixty-nine (79%) pts had ASCT, and overall response rate (ORR, partial response or better) post ASCT was 73%. For pts with HR FISH (defined as t(14;16), p53 del, 1q21 gain or 1p del) compared to SR FISH, the ORR post ASCT was 70% vs 77% (p = 0.67). OS from diagnosis was 93% at 3 years, 74% at 4 years and 51% at 5 years. Seven patients (8%) developed plasma cell leukemia, and there was no association between HR and SR FISH (p = 0.66). In multivariate analysis, ISS stage was an independent risk factor for mortality; pts with stage 3 had 7.3 times (CI: 1.16-36.4) and 5.7 times (CI: 1.63-20.0) the risk of mortality than pts with stage 1 and 2. Having an ASCT reduced mortality by 87% (CI: 0.04-0.41). Conclusions: Despite the use of novel therapies the OS at 5 years of our pts with MM was not significantly improved compared to SEER data from 1992-2013 (51% vs 48.5%). Pts with t(11;14) who had ASCT had increased survival compared to those who did not. Our results suggest that t(11;14) may confer a worse prognosis. Further prospective studies evaluating the risk of t(11;14) are warranted.

Practice patterns and clinical outcomes of therapy-related acute myeloid leukemia (TAML) in the US.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18139-e18139 ◽  
Author(s):  
Manisha Pant ◽  
Smith Giri ◽  
Prajwal Dhakal ◽  
Vijaya Raj Bhatt
Keyword(s):  
Clinical Trials ◽  
Regression Model ◽  
Older Patients ◽  
Cox Regression ◽  
Single Agent ◽  
National Database ◽  
Cell Transplant ◽  
Cox Regression Model ◽  
Comorbidity Burden ◽  
Multiagent Chemotherapy

e18139 Background: tAML, compared to de novo AML, has higher adverse features and a shorter overall survival (OS). The use of chemotherapy and hematopoietic cell transplant (HCT), and OS of tAML outside of clinical trials has not been studied well. Current study was designed to identify the treatment patterns and OS of tAML based on a national database. Methods: A total of 1,611 cases of tAML were identified between 2001-2011 using the National Cancer Database (NCDB). Data on age, race, gender, income, insurance and educational status, Charlson comorbidity index (CCI), receipt of chemotherapy and HCT were abstracted. Log-rank test was used to test equality of survivor function among the variables. Factors that attained statistical significance during bivariate analysis were factored into multivariate analysis using Cox Regression model. Results: Median age at diagnosis was 63 years (range 18-90), with 54% < 65 years, 59% females and 80% Caucasians. 67% underwent chemotherapy (20% single agent, 45% multiple agents and 2% unknown). 19% received HCT. Median OS was 6.7 months (m) with 1-year OS of 33%. Median OS was lower among patients ≥65 versus < 65 years (4.1 vs. 9.5 m; p < 0.001), those with higher comorbidity burden (7.8 m for CCI of 0, 6.0 m for CCI of 1, and 3.8 m for CCI of 2; p < 0.001), and diagnosed before versus during/after 2008 (5.6 vs. 7.7 m, p = 0.05). Median OS was higher among patients who received chemotherapy (8.4 vs. 3.7 m; p < 0.001) and HCT (22.6 vs. 4.9 m, p < 0.001), as compared to those who did not. Cox regression model showed the predictors of OS to be: receipt of HCT (hazard ratio, HR 0.36); use of multiagent chemotherapy (HR 0.80); age≥65 years (HR 1.25), higher comorbidities (HR of 1.21 for CCI of 1, and 1.45 for CCI of 2) and diagnosis on or after 2008 (HR of 0.81). Conclusions: Over half of patients with tAML are younger adults ( < 65 years), however, the receipt of chemotherapy and HCT is relatively low. OS is poor in general but improves with the use of multiagent chemotherapy and HCT. OS is worse in older patients and those with comorbidities. Given a dismal prognosis, older patients may be managed by leukemia team with expertise in geriatric oncology and should be encouraged to participate in clinical trials of novel therapies.

scholarly journals Elotuzumab As Post-Autologous Stem Cell Transplant Consolidation in Patients with High-Risk Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3141-3141 ◽  
Author(s):  
Nikhita Gadi ◽  
Linda Schmidt ◽  
Jaeil Ahn ◽  
Tianmin Wu ◽  
Scott D. Rowley ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Ultra High Risk ◽  
Equity Ownership ◽  
Baseline Characteristics

Introduction: Patients (pts) with high-risk multiple myeloma (HRMM) experience early disease progression post autologous stem cell transplant (ASCT). The median progression free survival (PFS) for HRMM pts undergoing ASCT with lenalidomide (len) maintenance ranges between 27 and 42 months in high risk pts and 22 months in ultra-high risk, defined by two or more adverse cytogenetic abnormalities such as: gain(1q), t(4;14), t(14;16),t(14;20), or del(17p)( Chakraborty et al, Leukemia,2018 and Jackson et al, Lancet, 2018). Elotuzumab, a humanized IgG kappa monoclonal antibody against SLAM-F7 (CS-1), is approved in combination with len and dexamethasone (ERd) in pts with relapsed MM (Dimopoulus et al, BJH, 2017). It directly activates natural killer (NK) cells and mediates myeloma cell death by antibody-dependent cell mediated cytoxicity. We hypothesized that administration of ERd as post-ASCT consolidation will enhance an immune-competent phenotype, by restoring NK cells and effector T-cell populations at a time of maximal disease de-bulking, and will ultimately improve outcomes among pts with HRMM. Methods: Thirty-one HRMM patients who achieved stable disease or better were treated beginning at 30-90 days post ASCT with ERd (29/31 pts) or elotuzumab/pomalidomide )/dex (EPd) (2/31 pts) between September 2016 and February 2019. With institutional review board approval, electronic medical records were reviewed for baseline characteristics, treatment history, adverse events (AE) while on therapy as defined by common terminology criteria for adverse events (CTCAE), and survival outcomes. Treatment with ERd or EPd was administered for 4 consecutive 28-day cycles per standard dosing regimens with a tapering or discontinuation of corticosteroids per investigator discretion with cycles 3 and 4. HRMM was defined by any of the following: ISS or Revised-ISS stage 3, CD-138 selected FISH with del 17p, 1q21 gain, t(4;14), t(14;16), and t(14;20), cytogenetics with 13q del or complex karyotype, and/or high-risk gene expression profile score. Ultra-HR pts were defined by having both del 13q and 1q21 gain by FISH based on recent unpublished COMPASS data. Minimal residual disease (MRD) was evaluated upon achievement of very good partial remission or complete remission using 10-color multiparametric flow cytometry. PFS was measured using the log-rank test. Response criteria was defined per International Myeloma Working Group criteria. Results: Baseline characteristics of all 31 patients are shown in Table 1. Thirty-four percent were ISS-3, 71% (22/31 pts) had high-risk FISH, of which 19% were ultra-high risk (6/22 pts). Seven pts (22.6%) underwent tandem-ASCT pre-consolidation. Of the 8 pts who had GEP testing, 2 (25%) were high risk. Best response to treatment by cycle is depicted in Table 2. Consolidative ERd/EPd deepened response compared to post-ASCT with 71.4% vs 19.4% achieving stringent complete remission (sCR). Post-consolidation, 19.3% vs 12.9%, pre-consolidation, achieved MRD negativity. With a median follow-up of 24.8 months, median PFS was 31.4 months (Figure 1). There was no significant association between median PFS and variables such as tandem ASCT and ultra-HR using multivariate cox regression. Although all pts experienced at least one AE while on therapy, only 1 patient (3.22%) experienced a grade 3 AE. Hematologic AEs included: anemia (48%), neutropenia (45%), and thrombocytopenia (52%), while the most common non-hematologic AEs included: fatigue (32%), malaise (23%), and back pain (19%). One patient experienced a serious AE (SAE) which was PCP pneumonia requiring hospitalization, resulting in early discontinuation from therapy. There was no treatment-related mortality. Conclusion: ERd or EPd as 4 months of fixed duration consolidation therapy post-ASCT resulted in a median PFS of 31.4 months amongst pts with HRMM, similar to or perhaps surpassing historical reports of HRMM pts receiving lenalidomide maintenance until progression. This therapy may offer comparable, if not superior, outcomes while having the advantage of allowing for significant time without therapy and perhaps improving quality of life and financial toxicity. This study is limited due to its retrospective nature. Larger prospective studies evaluating fixed duration ERd/EPd in HRMM patients post ASCT should be conducted. Disclosures Rowley: Allergan: Equity Ownership; Fate Therapeutics: Consultancy. Goldberg:COTA: Equity Ownership; Bristol-Myers Squibb: Consultancy; Cancer Outcomes Tracking and Analysis (COTA) Inc.: Equity Ownership. Siegel:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb Company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Biran:Bristol Meyers Squibb: Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Merck: Research Funding.

Second Autologous Stem Cell Transplant (ASCT) as Salvage Therapy in Patients with Relapsed Multiple Myeloma: Improved Outcomes in Patients with Longer Disease Free Interval after First ASCT.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 946-946 ◽  
Author(s):  
Joseph R. Mikhael ◽  
Sahar Zadeh ◽  
Sara Samiee ◽  
Keith Stewart ◽  
Christine Chen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Salvage Therapy ◽  
Median Overall Survival ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Disease Free Interval ◽  
Free Survival ◽  
Free Interval ◽  
Disease Free

Abstract Background: Single autologous stem cell transplant (ASCT) is considered the standard of care for younger multiple myeloma (MM) patients (pts). However, it is not curative and virtually all patients will ultimately relapse. As more options, such as biological therapy, are available to treat relapsed disease, the role of a second ASCT as salvage therapy is unclear. Method: Retrospective review of all MM pts who received a 2nd ASCT as salvage therapy at Princess Margaret Hospital. Results: Between February 1997 and June 2007, 61 MM pts received a second ASCT for relapsed MM at our institution. Median age was 56 yrs (range 35–71) at second transplant. 37 pts (61%) were male. Immunoglobulin subtype included IgG (36), IgA (14), light chain (6), nonsecretory (3), IgM(1) and IgD (1). Transplant conditioning regimen for first transplant was high dose melphalan (MEL) 140–200 mg/m2 in 51, MEL/etoposide(E)/TBI in 4, and MELl/TBI in 2. 2nd ASCT conditioning consisted of MEL + TBI +/− E in 2, MEL alone in 58 and Busulfan/Cyclophosphomide in 1. The median time from diagnosis to first transplant was 9.7 months (2.0–74.2). The median time to relapse after the first transplant was 32.6 months (9.7–85.6), with a median interval between transplants of 45.1 months (19.7– 115). Two transplant-related deaths occurred (3%). Response to first transplant was 4 CR (8%), 34 PR (68%), 2 MR (4%) and 10 SD (20%). Nineteen pts went on to maintenance therapy between transplants. Response to second transplant was 4 CR (8%), 41 PR (80%), 5 SD (10%) and 1 PD (2%). Median progression-free survival (PFS) was 15.8 months (0–63.8) while median overall survival (OS) was 4.2 years (0–7.0) after 2nd ASCT. The relationship between progression-free interval after 1st ASCT and the outcome of the 2nd ASCT is summarized Table 1. Patients can be stratified into two groups, those with a disease free interval of less than or greater than 24 months. The use of maintenance therapy did not differ between the two groups, 6 (40%) in patients with PFS ≤24 months and 13 (28%) in patients with PFS >24 months. Conclusions: 2nd ASCT is a feasible and safe salvage therapy in patients with relapsed MM. 2nd ASCT is effective in providing a median progression free survival of 1.25 years and median overall survival of 4.2 years after 2nd ASCT - results that compare favourably with other salvage approaches. Patients with a longer disease free interval after 1st ASCT experience a better progression free survival and overall survival after 2nd ASCT. It is reasonable, therefore, to consider a 2nd ASCT if the time to progression is greater than 2 years after first ASCT. Outcomes Based on Time to Progression Post 1st ASCT PFS post 1st ASCT # of pts median PFS post 2nd ASCT PFS post 2nd ASCT1 Median OS post 2nd ASCT OS post 2nd ASCT2 1 p< 0.005, 2 p< 0.05 ≤24 months 15 12.7 months 1 year: 46% 3.5 years 1 year: 85% 2 year: 11% 2 years: 76% 3 years 0% 3 years: 63% 4 years: 31% > 24 months 46 19.8 months 1 year: 74% 5.9 years 1 year: 91% 2 year: 45% 2 years: 82% 3 year: 31% 3 years: 65% 4 years: 55%

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