High Rate of Complete Remission (CR) and Upgraded Response with Weekly Maintenance Bortezomib Post Single Autologous Peripheral Stem Cell Transplant (PSCT) In Patients with Multiple Myeloma. Results of a Phase II Prospective Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2399-2399 ◽  
Author(s):  
Firoozeh Sahebi ◽  
Amrita Krishnan ◽  
Leonardo Farol ◽  
Ji-Lian Cai ◽  
George Somlo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Peripheral Neuropathy ◽  
Complete Remission ◽  
Partial Response ◽  
Maintenance Therapy ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Grade Iii

Abstract Abstract 2399 The quality and depth of response particularly achievement of complete remission (CR) have been associated with significant improvement in progression free survival (PFS) and overall survival in multiple myeloma patients undergoing autologous stem cell transplant. Achievement of CR is considered a valid surrogate endpoint for survival in clinical trials for patients with multiple myeloma. We performed a phase II study investigating the role of sequential bortezomib/dexamethasone followed by thalidomide/dexamethasone as maintenance therapy post single autologous PSCT. The objectives were to examine the feasibility, toxicities, CR, PFS and overall survival rates. Within 4–8 weeks of autologous PSCT using melphalan 200mg/m2, pts received weekly bortezomib (bor) at 1.3mg/m2 /wk × 3 weeks with 1 week rest and dexamethasone (dex) at 40mg/d × 4 d for 6 months, followed by thalidomide (thal) at 50 –200mg/d and dexamethasone (dex) at 40mg/dx4 d for 6 more months. Single agent thalidomide was then continued until disease progression. Between March 2008 and June 2010, forty-five pts were enrolled. Median age was 54 years (29-71). Median time from diagnosis was 6.1 mo. (3.5 – 145.9). Disease stage at diagnosis; by Salmon-Durie (I/II/III 2/8/34/1 not available) and by ISS (I/II/III 18/14/8/ 5 not available). Pts received prior induction treatment with thal/dex (15), bortezomib based (27) and lenalidomide based regimens (10). Median B2M at enrollment was 1.8 mg/L (1.05 -5.3). Disease status at enrollment included complete remission (CR) (11), very good partial response (VGPR) (11), partial response (PR) (23). Six pts had chromosome 13 abnormalities (1 pt by karyotype and 5 pts by FISH), 2 pts had t 4;14 (one with concurrent ch 17 p del) and 3 pts had complex cytogenetic abnormalities. Results: Forty-five pts have been enrolled and undergone transplant. Five pts were unable to start planned maintenance therapy due to development of grade II or more neuro toxicities (4), and persistent thrombocytopenia (1) after PSCT. Thirty nine pts started maintenance bor/dex within 4–8 weeks of PSCT. One pt is too early for maintenance therapy. Twenty-five pts have completed the planned 6 months of bor/dex. Ten pts stopped bor/dex because of low WBC (2), PN (4), diagnosis of adrenal cancer (1), myocardial infarction (MI) (1), and relapse (2). Six pts are still receiving maintenance bortezomib. With a median F/U of 8.5 mo. (0.2 -24.0) twelve of 44 evaluable pts (27%) have achieved CR post PSCT and 17 of 33 evaluable pts (51%) have achieved CR after bor/dex on an intention to treat (ITT) analysis. Fifteen of 25 pts (60%) who have completed 6 months of bor/dex have achieved CR. Nine of 25 pts (36%) have upgraded their response with bor/dex. Eight pts (24%) could not complete bortezomib due to toxicities. At one year post PSCT fourteen of 28 evaluable pts (50%) remain in CR. Six pts have relapsed of whom 2 died of relapsed myeloma (leptomeningeal disease 1 pt). One pt experienced MI while receiving bortezomib (grade IV). Grade III toxicities have occurred in 17 pts; low platelet (1), asthenia (2), mood alteration (1), GI (severe constipation due to partial bowel obstruction on thalidomide) (1), skin rash (1), hyperglycemia (1), lymphopenia (10), sinus bradycardia (1), elevated triglyceride (1), DVT (1), low phosphate (3), leukopenia (1), edema (1). Sixteen pts had peripheral neuropathy (PN) grade I prior to start of bortezomib. Only 8 pts have developed new PN on the study and all are grade I-II. No patient has experienced grade III-IV PN. Median bortezomib dose is 1.3 mg /m2 per week. Conclusion: Prolonged weekly bortezomib maintenance therapy is well tolerated and can upgrade response post single autologous PSCT with no severe peripheral neuropathy. Fifty one percent of pts have achieved CR and 36% have upgraded their response after six months of bortezomib/dexamethasone therapy suggesting this is an active maintenance strategy post PSCT. Disclosures: No relevant conflicts of interest to declare.

A Phase II Study of Sequential Velcade/Thalidomide/ Dexamethasone (VTD) as Maintenance Therapy Post Single Autologous Peripheral Stem Cell (PSCT) in Patients with Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3403-3403
Author(s):  
Firoozeh Sahebi ◽  
Amrita Krishnan ◽  
George Somlo ◽  
Leslie Popplewell ◽  
P. Parker ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Peripheral Neuropathy ◽  
Maintenance Therapy ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Disease Stage ◽  
Cell Transplant ◽  
Grade Iii

Abstract Abstract 3403 Poster Board III-291 Autologous PSCT remains standard treatment in younger patients (pts) with multiple myeloma. However, relapse is the major cause of treatment failure. Several studies have reported improved progression-free survival (PFS) and possibly overall survival with thalidomide alone or in combination with steroid and chemotherapy as maintenance/consolidation therapy post autologous PSCT. We performed a phase II study investigating the role of sequential velcade/thalidomide/dexamethasone (VTD) as maintenance therapy post single PSCT. The objectives were to examine the toxicities of prolonged course of sequential VTD, CR rate, PFS and overall survival following single autologous PSCT. Within 4-8 weeks of autologous PSCT using melphalan 200mg/m2, pts received weekly velcade (vel) at 1.3mg/m2 /wk x 3 weeks with 1 week rest and dexamethasone (dex) at 40mg/d x 4 d for 6 months, followed by thalidomide (thal) at 50 -200mg/d and dexamethasone (dex) at 40mg/dx4 d for 6 more months. Single agent thalidomide was then continued until disease progression. Twenty-eight pts have been enrolled. Median age is 54 years (29-66). Median time from diagnosis is 7.9 mo. (4.2 – 145). Disease stage at diagnosis; by Salmon-Durie (II/III 6/22) and by ISS (I/II/III 11/9/7/missing data in 1 pt). Pts received induction treatment with thal/dex (14), velcade based (15) and revlimid based regimens (7). Median B2M at enrollment is 1.75 mg/L (1.14 -5.3). Disease status at enrollment; CR (7) VGPR (9), PR (11), SD (1). Three pts have chromosome 13 abnormalities (1 pt by karyotype and 2 pts by FISH). Results: All pts have undergone transplant. Four pts were unable to start planned maintenance therapy due to development of grade II or more neuro toxicities (3), and persistent thrombocytopenia (1) after PSCT. Twenty-four pts started maintenance vel/dex within 4-8 weeks of PSCT. Nine pts have completed 6 months of vel/dex. Two pts stopped vel/dex because of low WBC (1) or PN (1). With a median F/U of 5.2 mo. (1.2 -17.3) nine of 28 pts (33%) have achieved CR post PSCT and six out of 11 evaluable pts (55%) have achieved CR after vel/dex. Six out of 9 pts (66%) who have completed 6 mo. of vel/dex achieved CR. Two out of 9 pts (22%) have upgraded their response with vel/dex. Four pts have completed 6 month of thal/dex and are beyond 1 year post PSCT. Two out of 4 pts remain in CR at one year post PSCT. One pt is in PR and 1 pt has progressed. Two pts could not complete thal/dex phase of therapy because of relapse (1) and grade III GI toxicity (1). Three pts have relapsed of whom 1 pt died of relapsed myeloma (leptomeningeal disease). No grade IV toxicity has been noted. Grade III toxicities have occurred in 4 pts; low platelet (1), fatigue (1), mood alteration (1), GI (severe constipation) (1). Thirteen pts have peripheral neuropathy (PN). Ten pts had PN grade I at enrollment. Only 3 pts have developed PN on the study and all are grade I - II. Median velcade dose is 1.3 mg /m2/wk and thalidomide dose is 100mg /d. Conclusion: Prolonged sequential velcade/thalidomide/dexamethasone maintenance therapy post single autologous PSCT is well tolerated with no severe peripheral neuropathy. Fifty-five percent of pts have achieved CR and 22% have upgraded their response after six months of velcade/dexamethasone therapy suggesting this is an active and well tolerated maintenance strategy post PSCT. Disclosures: Sahebi: Celgene: Honoraria; Millennium Pharmaceutical: Research Funding. Off Label Use: The use of bortezomib(Velcade)in combination with thalidomide and dexamethasone is investigated as maintenance therapy post autologuous stem cell transplant in patients with multiple myeloma.

Upfront Tandem Autologous Stem Cell Transplant Is Superior to Autologous or Allogeneic Stem Cell Transplant After Failure of a 1st Autologous Transplant,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4094-4094 ◽  
Author(s):  
Adrian Wong ◽  
Charles F. LeMaistre ◽  
Paul Shaughnessy ◽  
Carlos Bachier
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Complete Remission ◽  
Maintenance Therapy ◽  
Partial Remission ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Factors Affecting ◽  
Cox Regression Analysis

Abstract Abstract 4094 Disease progression remains the main cause of treatment failure after autologous stem cell transplant (SCT) in patients with multiple myeloma (MM). It is unclear what is the best salvage therapy after failure of a 1st autologous SCT in MM. We performed a retrospective study comparing 2nd autologous (auto-auto) versus 2nd allogeneic (auto-allo) SCT in patients progressing or relapsing after their 1st autologous SCT and compare their outcomes with patients receiving sequential planned double autologous (tandem) SCT as part of their upfront therapy for MM. The data was collected from CIBMT reports and medical records at Texas Transplant Institute from 2001 to 2010. Patient's characteristics and outcomes are described in table 1. Response to 1st and 2nd SCT was determined at 100 days post transplant and classified as good (stringent complete remission [sCR], complete remission [CR], very good partial remission [VGPR]) or poor (partial remission [PR], stable disease [SD] or progressive disease [PD]). All patients in the auto-allo group received a reduced intensity regimen. 20% of the patients in the auto-auto group received maintenance therapy after their 1st transplant with either thalidomide or lenalidomide and 10% of the patients in the auto-allo group received maintenance therapy after their 1st transplant either with thalidomide. None of the patients in the tandem group received maintenance therapy. The overall survival was calculated from the date of the 2nd transplant to the known date of death in all groups. Patients in the auto-allo group (15.9 months) had a worse median survival than in the auto-auto group (39 months) with both of them having a worse survival compared to patients undergoing tandem transplants (64.3) (p value = 0.003) (FIGURE).Table:PATIENT CHARACTERISTICS AND OUTCOMESTandem (n=29)Auto-Auto (n=32)Auto-Allo (n=10)Median age, years (range)62 (41–78)62.5 (45–81)54 (43–63)Median days from diagnosis to 1st transplant224.5 (93–1344)226 (117–1074)254.5 (101–416)Median days from 1st to 2nd transplant149 (99–189)847 (210–4158)350 (88–1281)Median total CD34+ cell infused 1st transplant3.29 (2–12)5.87 (2–28)6.03 (2–14)2nd transplant3.22 (2–9)4.47 (2–19)5.25 (3–11)Median WBC engraftment11 (9–13)11 (9–47)N/AMedian Platelet engraftment16 (10–19)15 (10–23)N/ACytogenetics High Risk17%3%10%ISS at 1st transplant I31%41%40%II34%12%0III14%6%10%ISS at 2nd transplant I48%53%40%II17%9%0III10%13%10%Response to 1st transplant Good10%63%70%Poor80%25%20%Response to 2nd transplant Good52%47%30%Poor41%41%70%Median Followup (months)57.1 (3.4–76.7)24.6 (10.5–87.8)48.0 (31.9–64.0)Maintenance Therapy after 1st transplant028%10%Figure:OVERALL SURVIVALFigure:. OVERALL SURVIVAL Forward stepwise Cox regression analysis was used to measure factors affecting overall survival. Factors used for analysis included age, cytogenetics (high risk = mutated p53, t(14;16), t(4;14), del 13), International Staging System (ISS) before 1st and 2nd SCT, use of maintenance therapy after 1st SCT, days from diagnosis to 1st SCT and days from 1st to 2nd SCT, CD34+ cells infused at 1st and 2nd SCT. Age and ISS of III at 2nd transplant were identified as factors affecting survival in the auto-auto group (hazard ration of 1.081 and 5.700, respectively). In conclusion, overall survival after salvage from 2nd autologous stem cell transplant is longer than after a 2nd allogeneic transplant. Upfront, planned tandem autologous stem cell transplant is superior to both salvage strategies. Larger, randomized trials are needed to confirm these results. Disclosures: Shaughnessy: Otsuka: Honoraria, Speakers Bureau; Millenium: Honoraria, Speakers Bureau; Genzyme: Honoraria, Speakers Bureau.

Local Experience with Autologous Stem Cell Transplant in Multiple Myeloma at a Public Institution (Instituto Nacional de Cancerologia)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5504-5504
Author(s):  
Eduardo Cervera ◽  
Jorge Carlos Torres ◽  
Nidia P. Zapata ◽  
Juan Rafael Labardini ◽  
Jose Ramiro Espinoza ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Complete Remission ◽  
Partial Response ◽  
Stem Cell Transplant ◽  
Conflicts Of Interest ◽  
Autologous Stem Cell Transplant ◽  
Public Institution ◽  
Cell Transplant ◽  
Good Partial Response

Abstract Introduction. Autologous stem cell transplant is considered the standard of care in young (<70) fit patients with Multiple Myeloma. We know that intensive chemotherapy or stem cell transplant do not produce a cure, but it does prolong event free survival and overall survival. The aim of this study is to report 15 years of experience in stem cell transplant at the Multiple Myeloma (MM) clinic at Instituto Nacional de Cancerologia (INCan). This is a retrospective, observational trial, we reviewed clinical and electronic files of patients that received an autologous stem cell transplant between January 1st of 2005 and March 1 2015. We assessed clinical status, demographic variables, disease status and clinical outcome of the patients that were included in the study. 48 patients were included into the study, 25 males and 23 females, we grouped the patients according to age, <35 years (2 patients), <50 years (14 patients), 50-65 years (31 patients), >65 years (1 patient). 34 patients had a normal karyotype, 4 had 13q14, 2 had MLL deletion and 8 did not had a karyotype performed. According to the M component we had 6 IgA patients, 32 IgG, 1 IgM, 1 Kappa, 5 lambda, 2 non secretory and 1 combined. According to ISS, 34 patients were assigned a ISS of 1, 10 a SS of 2, and 4 a ISS of 3. The majority of our patients were transplanted within the first line of treatment, 2 within the second line and none with more than 2 lines of treatment. 20 patients that received thalidomide plus dexamethasone achieved complete remission prior to transplant. 14 patients received thalidomide plus dexamethasone achieved very good partial response. 4 patients that received bortezomib plus thalidomide or dexamethasone achieved complete remission prior to transplant. 4 patients received bortezomib plus thalidomide or dexamethasone achieved very good partial response prior to transplant. 3 patients that received two lines of treatment achieved complete remission prior to transplant. 3 patients achieved very good partial response prior to transplant and received more than two lines of treatment. Time from diagnosis to transplant had a mean time of 17.4 months, with 6-12 months as the most prevalent group with 20 patients, followed with 13 patients in the 12-24 months window. 17 tandem transplants were performed. From the 25 patients that received a ASCT and were in CR, 19 maintained that response, from the 23 patients that achieved VGPR 20 maintained that response, 1 achieved partial response (PR), 4 had stable disease, and 4 had progression of the disease. We are looking forward to presenting the full data of our analysis. Since our casuistry does not differ from the international reports. Disclosures No relevant conflicts of interest to declare.

Influence of Race on Outcomes in Multiple Myeloma Patients with Renal Dysfunction Undergoing High Dose Therapy Followed By Autologous Stem Cell Transplant

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5904-5904
Author(s):  
Lakshminarayanan Nandagopal ◽  
J. Christine Ye ◽  
Marie Ventimiglia ◽  
Muneer H. Abidi ◽  
Lois Ayash ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Maintenance Therapy ◽  
Renal Dysfunction ◽  
Stem Cell Transplant ◽  
Disease Status ◽  
Patient Characteristics ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant

Abstract Approximately 20% of Multiple Myeloma (MM) patients (pts) have renal dysfunction(RD) at the time of diagnosis and some more may develop it during the course of their disease. Autologous stem cell transplant (ASCT) is a treatment modality for this incurable malignancy and there are ongoing studies to determine the optimal timing of ASCT in this disease. There are conflicting data regarding the outcomes among different racial groups with regards to ASCT in MM. In this restrospective review we studied outcomes in pts of different races with RD undergoing ASCT for MM. Between June 2005 and December 2013, we identified 107 pts with MM with RD (creatinine clearance < 60 ml/min/1.73 m2) who were not on hemodialysis and underwent ASCT at our institution. Of the 107 pts, 76 were caucasian(C) pts and 31 were identified as other (O) races (25 African American, one Hispanic, two Middle-eastern, three Asian). The patient characteristics of both groups are shown in Table 1. There were no statistically significant differences in the characteristics between the 2 groups. Approximately a quarter of the pts received their melphalan dose on the inpatient unit in both groups. During the hospitalization all pts received G-CSF from Day +6 till absolute neutrophil count ≥ 1500/µl and antimicrobial prophylaxis with norfloxacin, acyclovir and fluconazole. The median follow up was 35.9 months (range, 5.1-106.3). One patient in the C group died 98 days after ASCT and had evidence of disease progression. There were no deaths in the O group during the 100 days after ASCT. Table 2 shows post ASCT disease status and details about post ASCT maintenance therapy. There were no statistically significant differences between the groups in disease status or change in disease status at day 100 post ASCT. Although more patients in the C group received maintenance therapy post ASCT, this difference was not statistically significant. Figures 1 and 2 show the relapse free survival (RFS)and overall survival (OS) of both groups. The median RFS for C and O groups were 32.3 and 20.9 months (p =0.63, log rank), respectively. The median OS of the C and O groups were 73.1 and 47.8 month (p=0.31, log rank), respectively. Our limited experience suggests that there was no effect of race in the post ASCT outcomes for MM pts with RD. ASCT was safe with acceptable transplant related mortality and good long -term outcomes for MM pts with renal dysfunction. Table 1: Patient Characteristics (N=107) Patient Characteristics Caucasians (n=76) Others (n=31) Median Age (range) 63 (36-73) 64(28-73) 0.58 Gender Male 42 (55%) 17 (55%) 0.9 Females 35 (45%) 14 (45%) Chemo regimens prior to ASCT 1 51 (67%) 21 (68%) 0.95 ≥ 2 25 (33%) 10 (32%) Agents used prior to ASCT IMid 12 (16%) 4 (13%) 0.85 PI 18 (24%) 9 (29%) Both 46 (60%) 18 (58%) Disease status at time of ASCT PD 7 (10%) 5 (16%) 0.35 SD 9 (12%) 4 (13%) PR 20 (26%) 11 (35%) VGPR 20 (26%) 8 (26%) CR 20 (26%) 3 (10%) Median creatinine clearance (range) 45.5 (15-60) 43 (21-60) 0.35 Subtype* IgG Kappa 29 (34%) 18 (58%) 0.25 IgG Lambda 18 (24%) 6 (19%) Ig A Kappa 9 (12%) 2 (6%) Ig A Lambda 5 (7%) 3 (10%) K Light Chain 6 (8%) 0 L Light Chain 5 (7%) 0 Non- Secretory 3 (4%) 2 (6%) Cytogenetic Risk Standard 65 (85%) 18 (58%) 0.67 High Risk 5 (7%) 2 (6%) Median Melphalan Dose mg/m2 (range) 140 (140-200) {140(58),160(5), 180(4),200(9)}® 140 (100-200) {100(2),140(25), 200(9)} 0.89 Administration of Melphalan Inpatient 18 (24%) 9 (29%) 0.56 Outpatient 58 (76%) 22 (71%) Median CD 34 Cell dose x106/kg (range) 3.3 (2 -10.1) 3.9 (2.3-9.5) 0.34 Median Engraftment Day (range) Neutrophil 12 (11-20) 12(10-27) 0.86 Platelets 18(11-88) 17 (11-42) 0.10 Median Days of Hospitalization (range) 15 (9-65) 16 (12-55) 0.96 * 1 pt each in the caucasian group had IgD Lambda and IgM Kappa paraprotein ® Pts received 160 and 180 mg doses as part of a study PI: proteosome inhibitors, PD: progressive disease, SD: stable disease, PR: partial response, VGPR: very good partial response, CR: Complete response Table 2: Disease status at Day 100 post ASCT Caucasian (N=76) Other (N=31) P Value Disease Status CR 26 (34%) 6 (19%) 0.5 VGPR 20 (26%) 12 (38%) PR 17 (22%) 6 (19%) SD 7 (9%) 4 (13%) PD 2 (3%) 2 (7%) Not available 4 (6%) 1 (3%) Change in Disease Status Improved 23 (30%) 13 (42%) 0.66 Unchanged 45 (59%) 15 (48%) Worsened 4 (6%) 2 (7%) Not available 4 (6%) 1 (3%) Maintenance Therapy IMid 40 (53%) 9 (29%) 0.15 PI 2 (3%) 1 (3%) None 29 (38%) 19 (61%) Not Known 5 (7%) 2 (7%) Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Phase 2 Trial of LDE225 and Lenalidomide Maintenance Post Autologous Stem Cell Transplant for Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1905-1905
Author(s):  
Francis K. Buadi ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
Gabriela Perez ◽  
Morie A. Gertz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Maintenance Therapy ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Grade 3

Background: Lenalidomide maintenance therapy post-autologous stem cell transplantation (ASCT) is associated with improved progression-free survival (PFS) and possibly overall survival in multiple myeloma (MM). However, almost all patients do relapse as a result of residual multiple myeloma cells that remain after the high-dose chemotherapy. In the myeloma setting it has been found that the hedgehog (Hh) pathway is essential for maintaining a subset of tumor causing stem cells. LDE 225 (Sonidegib) is a potent selective oral bioavailable antagonist of Smoothened (SMO), a component of the Hh signaling pathway. In in vitro experiments, LDE225 treatment of myeloma cell lines resulted in a modest inhibition of cell proliferation at increasing doses. When LDE225 was combined with lenalidomide, a more than additive effect was observed in terms of cell proliferation, an effect that was more pronounced in the context of myeloma cell lines growing in co-culture with marrow derived stromal cells. These findings form the basis of evaluation of LDE 225 as a strategy to enhance the activity of lenalidomide in the post-transplant maintenance setting. The minimal residual state post SCT provides the most optimal situation for evaluation of a drug that is likely to work by inhibiting the tumor cells that escaped high dose therapy. Methods: Multiple myeloma patients without evidence of progression, who were 60 - 120 days after a single autologous stem cell transplant (SCT), performed within 1 year of diagnosis were eligible for the study. Maintenance therapy was started approximately 3 months after SCT. Treatment consisted of lenalidomide 10 mg days 1-21 and LDE225 400 mg days 1-28 in 28-day cycles for a total of 18 cycles. The goal of the study was to assess toxicity of this combination, complete response rate (CR) progression free survival (PFS) at 1 and 2 year and overall survival (OS). CR and PFS were estimated using an exact binomial distribution and Kaplan Meier curves respectively. Results: A total of 28 patients were accrued from Jan 2014 to Aug 2016, 1 patient canceled prior to treatment and 1 patient was deemed ineligible resulting in 26 evaluable pts for CR and PFS. The median age of all pts (n=26) was 60 years (range 43-69) and 50% were males. Seventy-three percent of patients reported one treatment regimen prior to SCT, while 27% reported 2 or more prior regimens. The other characteristics of the patient are summarized in Table 1. Twenty seven pts received at least one cycle of treatment and are evaluable for toxicities (AE). Patients were treated for a median of 12.5 (range 1-18) cycles. While 10 pts (38.5%) completed protocol treatment (18 cycles), the remaining 16 pts went off treatment due to AEs (6, 23%), disease progression (3, 11.5%), refusal of further treatment (3, 11.5%) and other reasons (4, 15.4%). A grade 3 or higher AE at least possibly attributed to either drug was seen in 63%. Grade 3+ hematologic toxicities were noted in 30%, with 7% neutropenia and 4% thrombocytopenia. Notable grade 2+ non-hematologic toxicities with more than 5% incidence were dysgeusia 22%, alopecia 11%, and anorexia 7%. Grade 3+ non-hematologic toxicities were fatigue, myalgia and arthralgia each at 7%. The CR rate in evaluable patients was 46% (5 CRs and 7 sCRs) with a 95% CI of 27% - 66%. CR rate improved from 31% to 46%. VGPR or better improved from 42% to 85%. The 24-month PFS (time from SCT to progression or death due to any cause) was 73% (95% CI: 57.9 - 92.3%) with a median time to censoring of 38 months. Conclusion: Lenalidomide in combination with LDE225 as posttransplant maintenance therapy was associated with some toxicity but manageable. The combination improved the depth of response after autologous stem cell transplant. Long-term follow-up is needed to determine overall survival. Disclosures Lacy: Celgene: Research Funding. Dispenzieri:Celgene: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Janssen: Consultancy; Intellia: Consultancy; Akcea: Consultancy; Alnylam: Research Funding. Gertz:Ionis: Honoraria; Alnylam: Honoraria; Prothena: Honoraria; Celgene: Honoraria; Spectrum: Honoraria, Research Funding; Janssen: Honoraria. Kapoor:Glaxo Smith Kline: Research Funding; Amgen: Research Funding; Janssen: Research Funding; Cellectar: Consultancy; Takeda: Honoraria, Research Funding; Celgene: Honoraria; Sanofi: Consultancy, Research Funding. Dingli:alexion: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Rigel: Consultancy; Karyopharm: Research Funding. Russell:Imanis: Equity Ownership. Kumar:Janssen: Consultancy, Research Funding; Takeda: Research Funding; Celgene: Consultancy, Research Funding. OffLabel Disclosure: Sonidegib (LDE 225) is a selective oral bioavailable antagonist of Smoothened (SMO), a component of the hedgehog signaling pathway.

Lenalidomide maintenance after second autologous stem cell transplant improves overall survival in multiple myeloma

2020 ◽  
Vol 61 (8) ◽  
pp. 1877-1884 ◽  
Author(s):  
Dipenkumar Modi ◽  
Jie Chi ◽  
Seongho Kim ◽  
Lois Ayash ◽  
Asif Alavi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant

Tandem Autologous Stem Cell Transplantation in Chemorefractory Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4554-4554
Author(s):  
Catherine Garnett ◽  
Chrissy Giles ◽  
Osman Ahmed ◽  
Maialen Lasa ◽  
Holger W. Auner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Free Survival

Abstract Abstract 4554 High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is currently standard treatment for younger patients with multiple myeloma, resulting in improved survival and response rate compared to conventional chemotherapy. Disease relapse, however, remains almost inevitable and thus the role of two successive (tandem) autologous stem cell transplants has been evaluated in chemorefractory patients as a means of prolonging duration of disease response. We retrospectively analysed the results of nine patients with chemorefractory disease treated at a single UK institution who received tandem ASCT between January 1998 and February 2009. There were six men and three women. Median age at diagnosis was 56 years (range, 42–65 years). Paraprotein isotype was IgG in eight patients and IgA in one patient. Median serum paraprotein level was 41g/L (range 12–73g/L) at presentation. At time of 1st transplant six patients were in stable disease (SD) and three had evidence of progressive disease. Conditioning melphalan dose was 140mg/m2 in all but two patients who received 110mg/m2 and 200mg/m2. Median time between transplants was 3.7 months (range 2.3–6.4 months) with PR and SD being observed in 2/9 and 7/9 patients at time of 2nd transplant. None of the patients reached complete response (CR). One patient received melphalan 140mg/m2 prior to 2nd transplant. The remaining patients received melphalan 200mg/m2. Median follow up after tandem transplant was 54.3 months (range 15.6 –143.6 months). No treatment related mortality was reported. At the time of analysis, six patients were still alive and under follow up with an overall survival (OS) figure for the group of 52% at 10 years from diagnosis (Figure 1). Median progression free survival (PFS) was 20 months from 2nd transplant (range 6.7–62.6 months) (Figure 2). Tandem autologous stem cell transplant in chemorefractory patients has resulted in overall survival similar to autologous stem cell transplant in chemosensitive patients and should be considered in patients with chemorefractory disease. Figure 1: Overall survival from diagnosis in patients receiving tandem autologous stem cell transplant for multiple myeloma Figure 1:. Overall survival from diagnosis in patients receiving tandem autologous stem cell transplant for multiple myeloma Figure 2: Progression free survival following tandem transplant Figure 2:. Progression free survival following tandem transplant Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document