scholarly journals Pilot study of 13cis-retinoic acid+dexamethasone+alpha interferon as maintenance therapy following high-dose chemotherapy and autologous stem cell transplant for multiple myeloma

2005 ◽  
Vol 35 (10) ◽  
pp. 979-984 ◽  
Author(s):  
J Friedman ◽  
H Khoury ◽  
D Adkins ◽  
S Devine ◽  
B Nervi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Retinoic Acid ◽  
Pilot Study ◽  
Maintenance Therapy ◽  
Stem Cell Transplant ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant

Incidence of Adrenal Insufficiency in Patients with Multiple Myeloma during High Dose Chemotherapy and Autologous Stem Cell Transplant

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5862-5862 ◽  
Author(s):  
Ahmad Hatem Mattour ◽  
Shatha Farhan ◽  
Nalini Janakiraman ◽  
Edward Peres
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Adrenal Insufficiency ◽  
Stem Cell Transplant ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
Adrenal Function ◽  
High Dose ◽  
Cell Transplant ◽  
Cortisol Levels

Abstract Background High dose chemotherapy (HDC) followed by autologous stem cell transplant (ASCT) is considered the standard of care for patients with multiple myeloma (MM). With most patients receiving induction therapy that includes corticosteroids. The combined effect of prior therapy for myeloma and ASCT related complications may result in hypotension and require intensive medical treatment. To date the incidence of adrenal insufficiency in the setting of ASCT is unknown. The effects of this underlying disorder in regards to post transplant outcome remain unknown as well. We set out to compare the outcomes of patients with multiple myeloma who underwent ASCT with adrenal insufficiency compared to those with sufficient adrenal function. Methods We undertook a prospective study in 13 consecutive patients with Multiple Myeloma admitted for high dose chemotherapy and autologous stem cell transplant at Henry Ford Hospital between February 2014 through June 2014, with the first patient sample being obtained in on 2/14/2014 and last sample recorded in 6/23/2014. Random cortisol levels were obtained on the day of admission or day -2 (figure 1), prior to the start of high dose chemotherapy. All prior therapies included corticosteroids and consisted of the following RVD, DCEP, RD, VD, DT-PACE. Patients were classified into two groups those with cortisol levels > 5 and those patients who had cortisol levels <5. Endpoints analyzed included hypotension, septic shock, and duration of antibiotic therapy. Results Of the 13 patients analyzed the median age was 60 years old (range 53-78), gender 8 male patients 5 female. All patients underwent high dose chemotherapy with Melphalan and Autologous stem cell transplant. Of the 13 patients in which data was obtained 3/13 23% had adrenal insufficiency prior to high dose Melphalan and ASCT. With a median cortisol level of 3.2 in the patient cohort who were found to be adrenal insufficient. The incidence of hypotension was 2/3 66% in the adrenal insufficient patients compared 1/10 10% in the cohort with sufficient adrenal function. Septic shock occurred in 2/3 66% of the adrenal insufficient compared to 0/10 in the adrenal sufficient group. The median duration of antibiotic therapy was 5 days in the adrenal insufficient cohort compared to 2 days in the patients with adequate adrenal function. Conclusion In this small cohort of consecutive patients from a single center, we found that there was a high incidence of adrenal insufficiency 23% in patients undergoing ASCT. The treatment regimens varied in the study group with all patients receiving corticosteroid therapy in there induction regimen. Given the unexpectedly high incidence of adrenal insufficiency a consideration should be given to check a random cortisol level prior to the initiation of HDC. Supplemental therapy or treatment should be considered in this high risk group to avoid unnecessary complications and prolonged antibiotic use and supportive care in this patient cohort. Figure 1. Random Cortisol levels obtained prior to Autologous stem cell transplant Figure 1. Random Cortisol levels obtained prior to Autologous stem cell transplant Disclosures No relevant conflicts of interest to declare.

A Comparative Study Of The Outcome Of Isolated Chromosome 13q and Clonal Progression Detected By I-FISH Do Additional Cytogenetic Abnormalities Impact Survival In Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2160-2160
Author(s):  
Edward Peres ◽  
Shatha Farhan ◽  
Philip Kuriakose ◽  
Susan Michalowski ◽  
Alexandra Sitarik ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Cytogenetic Abnormalities ◽  
Chromosome 13Q

Abstract Background Chromosomal abnormalities detected by interphase fluorescence in situ hybridization (I-FISH) are an important prognostic marker in patients with multiple myeloma (MM). Isolated chromosome 13q has been considered standard risk when identified by I-FISH and high risk by conventional cytogenetics. The impact of additional cytogenetic abnormalities with chromosome 13q identified by I-FISH in regards to prognosis has not been fully defined. In this report, we describe the outcome of patient’s with multiple myeloma with isolated chromosome 13q and 13q+ (additional cytogenetic abnormalities) identified by I-FISH at our institution between January 2003 and January 2013 and had I-FISH analysis prior to treatment. Methods The primary objective was to compare patient’s outcomes in regards to response, time to progression, and overall survival between patients who had an isolated 13q and 13q+ identified by I-FISH in the bone marrow plasma cells. Kaplan & Meier curves were generated to calculate overall survival (OS) between the two groups. Results Between January 2003 and January 2013, we identified 76 patients by I-FISH who had either an isolated 13q or 13q+ in patients with multiple myeloma (Patient characteristics Table 1). Of the patients with an isolated 13q abnormality 33% received a bortezomib-based regimen and 38% in the 13q+ group. Of the patient’s with a isolated 13q 38% went onto receive high dose chemotherapy followed by autologous stem cell transplant (ASCT) while 20% with a 13q+ received ASCT. African American patients with 13q consisted of 65% and 60% with 13q+ in our patient population. For the 13q or 13q+ who underwent high dose chemotherapy followed by autologous stem cell transplant OS was 85% compared to the non-transplant group 45% (p=0.01) (Figure 2). On follow up at a median of 2.5 years mortality occurred in 31% of the 13q patients compared to 62% in the 13q+ group. The overall survival at 5 years was 25% in the 13q+ group compared to 65% in the patient’s with an isolated 13q, With the 13q+ group having an overall poor OS (p=0.03) Conclusion Patients who harbor the 13q and additional cytogenetic abnormalities identified by I-FISH have a significant worse outcome compared to patients with an isolated 13q. These patients should be considered high risk and consideration for treatment with novel agents and autologous stem cell transplant followed by post-transplant maintenance therapy should be considered. 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.

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