Outcome of Elderly Patients with Acute Myeloid Leukemia (AML) Post Hypomethylating Agent (HMA) Failure.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2627-2627 ◽  
Author(s):  
Koichi Takahashi ◽  
Hagop M. Kantarjian ◽  
Hady Ghanem ◽  
Farhad Ravandi ◽  
Jorge E. Cortes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Elderly Patients ◽  
Salvage Therapy ◽  
Research Funding ◽  
Objective Response ◽  
Induction Treatment ◽  
High Dose ◽  
Cell Transplant ◽  
Investigational Agents ◽  
The Impact

Abstract Abstract 2627 Background and Aims: HMA such as 5-azacitadine or decitabine have been increasingly used as induction therapy in elderly patients with AML. The prognosis of such patients who failed initial HMA and the impact of subsequent chemotherapy on outcome are unknown. Therefore the aims of the current analysis are 1) to evaluate the prognosis of elderly patients with AML post HMA failure and 2) to evaluate the efficacy of using intensive cytarabine-based salvage therapy vs. low intensity investigational therapy. Methods: We analyzed 54 patients older than 60 years old with AML who received induction treatment with HMA using either 5-azacitadine (n=17; 31%) or decitabine (n=37; 69%) under various clinical trials. Result: Median age of the group was 68 years (range; 60–84); 39% patients were female. Forty three patients (77%) had performance status (PS) ≤1 and 11 patients had PS of 2 (23%). Mean initial white blood cell count was 10.9 ± 3.2 (x103/μl), hemoglobin 9.9 ± 0.2 (g/dl), platelet count 77 ± 9 (x103/μl), and bone marrow blast count 44 ± 2.9 (%). Cytogenetic category was classified as intermediate in 30 (55%) patients and poor in 24 (45%) based on the MRC criteria. Six patients (11%) carried FLT3-ITD mutation and 1 carried FLT3 D835 mutation. Complete remission (CR) was achieved in 24 patients (44%) with median numbers of cycles required to achieve CR being 3 (range; 1–6). All patients received further salvage therapies, at the time of failure, with a median of 2.5 (range, 2–5) salvage regimens. As part of the salvage regimen, high-dose cytarabine-based regimen (HDAC) was given to 32 patients (59%). Objective response rate to HDAC was 53%, with 18 pts achieving CR. Median number of courses given was 2 (range, 1–7) with a median duration of response of 3 months. No induction death was reported. Stem cell transplant was performed in total of 9 patients (17%) as a consolidation post HDAC (n=4) or as salvage therapy (n=5). With a median follow-up of 5 months post HMA failure, 5 (9%) patients remained alive receiving therapy. The median overall survival (OS) was 5.4 months (range, 2.3–8.5). The 1-year overall survival rate was 26%. There was no difference in OS between patients who received HDAC versus those who received investigational agents (p=0.25). Conclusion: The outcome of untreated elderly patients with AML who failed HMA is poor with a median survival of 5 months. HDAC based regimen, although active with low treatment related morbidity, yielded no survival improvement compared to investigational agents. Such patients should benefit from more innovative approaches. Disclosures: Ravandi: Celgene: Honoraria, Research Funding; Eisai: Honoraria, Research Funding.

Do Elderly Myeloma Patients Benefit From High Dose Therapy (HDT) and Autologous Stem Cell Transplant (ASCT)?: A Comparative Survival Analysis using SEER Registry

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2072-2072 ◽  
Author(s):  
Eden Hailemichael ◽  
Jonathan L. Kaufman ◽  
Christopher R. Flowers ◽  
Edmund K. Waller ◽  
Mary Jo Lechowicz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Elderly Patients ◽  
Research Funding ◽  
Selection Process ◽  
Progression Free Survival ◽  
The Elderly ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Significant Survival

Abstract Abstract 2072 Introduction: Many randomized control trials demonstrated that HDT-ASCT is superior to conventional therapies in myeloma patients and prolongs progression free survival (PFS) and overall survival (OS) (Attal M, 1996, Childs JA, 2003). However, in treating a malignancy with a median age of diagnosis of 69 years, the majority of the patients will not be eligible for this beneficial approach if a nominal numerical age cut-off (<65 years) is followed based on the assumption that elderly patients cannot tolerate HDT-ASCT; nor will they be eligible for clinical trials involving HDT-ASCT if stringent age-restricted inclusion criteria are incorporated. Therefore, we have evaluated if the elderly patients benefit from HDT-ASCT. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) 18 registry data (www.seer.cancer.gov) as our comparator (reflects 28% of the US population);to provide information on incidence, prevalence and survival from 1973–2009. The data from an institutional cohort (IC) is obtained from the records of patients that underwent HDT-ASCT from January 2000 to January 2012. We used IBM SPSS version 20 to generate the Kaplan-Meier survival curves. Results: Of the 6,571,117 malignant cases listed in SEER registry, a total of 74,826 cases (1.1%) of multiple myeloma (ICD-03 code 9732) were identified (39735 males and 35091 females). Median age of the patients is 70 years. Among these patients 48,988 patients (65%) are over the age of 65. A total of 901 myeloma patients underwent HDT-ASCT from IC during the evaluable period and 167 patients (19%) were over the age of 65. The median survival for each subset is listed in Table 1. Both male and female WCI-ASCT myeloma patientshad prolonged OS compared to the SEER myeloma patients, despite the difference in magnitude of advantage in IC-ASCT male patients vs. female patients. Both white and black patients, as well as patients undergoing HDT-ASCT across all age subgroups had a significant survival advantage. Conclusions: In each subgroup, by the decade of diagnosis, gender, race, age subsets we have consistently demonstrated a significant survival benefit for IC transplant patients ≥age 65 compared to SEER myeloma patients ≥age 65 if offered HDT-ASCT. Selection-bias prevails in the groups showing improved overall survival. Hence, a careful selection process considering physiologic age as a determinant for transplant eligibility would result in better outcomes, and not preclude the elderly from the survival benefits of HDT-ASCT. Disclosures: Kaufman: Millenium: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Onyx: Consultancy. Flowers:Celgene: Consultancy; Prescription Solutions: Consultancy; Seattle Genetics: Consultancy; Millennium: Research Funding, Unpaid consultancy, Unpaid consultancy Other; Genentech: Unpaid consultancy, Unpaid consultancy Other; Gilead: Research Funding; Spectrum: Research Funding; Janssen lymphoma research foundation: Membership on an entity's Board of Directors or advisory committees. Waller:Outsuka: Research Funding.

Statins Use Improves the Clinical Outcomes of Salvage Therapy in Relapsed/Refractory CLL

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3931-3931
Author(s):  
Long Xuan Trinh ◽  
Young Kwang Chae ◽  
Preetesh Jain ◽  
Ohad Benjamini ◽  
Xuemei Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Elderly Patients ◽  
Clinical Outcomes ◽  
Salvage Therapy ◽  
Older Patients ◽  
Conflicts Of Interest ◽  
Young Patients ◽  
The Other ◽  
Concurrent Use ◽  
The Impact

Abstract Abstract 3931 Introduction - Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase. In addition, statins possess anti-inflammatory, immunomodulatory, antioxidant, and cell growth inhibitory properties. In B- CLL cells, statins induce in-vitro apoptosis (Daphne Chapman-Shimshon et-al), suggesting that statins might possess properties. We noticed a high prevalence of dyslipidemia in patients with chronic lymphocytic leukemia (CLL). However the impact of dyslipidemia and its modulation by statins on clinical outcomes of patients with CLL remains unclear. Therefore, we conducted a retrospective analysis to assess the effect of statins in patients with CLL who received salvage (fludarabine, cyclophosphamide and rituximab) FCR chemotherapy. Methods - We analyzed the clinical outcome of relapsed/refractory patients with CLL (n=284) who underwent FCR salvage therapy at our institution between 1999 and 2012. Patients who were uninterruptedly treated with statins at least one month prior to and during salvage therapy (n=35) were assigned to the statins arm, whereas the other arm consisted of 249 patients who were not treated with statins. The Cox proportional hazards regression model was used to assess the association between patient characteristics and progression-free survival (PFS) and overall survival (OS). Actual survival and PFS were estimated using the method of Kaplan-Meier, and OS and PFS were compared among two groups of patients using log-rank test. Results - All pretreatment characteristics of the patients with concurrent use of statins were similar to those who were not treated with statins except for their age. Patients in the statins arm were older: 21 patients (60%) were older than 65 compared to 74 patients of 249 (30%) in the other group (p<0.05). The median OS and PFS of all 284 patients were 3.9 years (95% CI: 3.4–4.5) and 1.74 years (95% CI: 1.6–2.3), respectively. PFS was significantly longer in patients treated with statins. Fifteen of the 35 statin-treated patients (43%) as opposed to only 36 of 249 (14%) in the non-statins group experience no disease progression. Concurrent use of statins significantly prolonged PFS. The median PFS for statin-treated v/s. untreated was 4.6 and 1.7 years, respectively (p<0.05). This significantly improved PFS was consistent in young and elderly patients. In young patients (age < 65) with statins, the median PFS was not reached whereas in patients who were not treated with statins it was 2 years (p<0.05). In older patients (age ≥ 65), PFS was significant longer with concurrent use of statins than without statins; estimated PFS were 2 and 1.6 years, respectively (p<0.05). With the median follow-up of 5 years, the median overall survival was significantly longer in patients treated with statins, with 17 of 35 (49%) patients of the statins group and 59 (24%) of 249 in patients who were not treated with statins alive at the end of study. Concurrent use of statins significantly prolonged OS with an estimated median OS for the two groups of 6.9 years and 3.9 years, respectively (p<0.05). This significantly improved OS was consistent in young and elderly patients. Young patients (age <65) with statins had a significant prolonged survival with an estimated OS of 8.6 years whereas estimated OS in young patients without statins (p<0.05) was only 4 years. In older patients (age ≥65) the median OS was significantly longer with the concurrent use of statins than without statins; estimated OS in the two subgroups were 6.9 and 2.6 years respectively, (p<0.05). Conclusions - In conclusion, concurrent use of statins significantly improved OS, PFS in relapsed/refractory CLL patients treated with salvage FCR therapy. Further studies to determine the role of statins and mechanism of action in patients with CLL are warranted. Disclosures: No relevant conflicts of interest to declare.

Phase 1 study to evaluate the safety and efficacy of immunotherapy with tremelimumab and durvalumab in multiple myeloma patients receiving high dose chemotherapy and autologous stem cell transplant (HDT/ASCT) + peripheral blood lymphocyte (PBL) reinfusion.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS8051-TPS8051 ◽  
Author(s):  
Alexander M. Lesokhin ◽  
David J. Chung ◽  
Hearn J. Cho ◽  
Lisa Shohara ◽  
Paul Schwarzenberger ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibody ◽  
Overall Survival ◽  
Residual Disease ◽  
Hematologic Malignancy ◽  
Phase 1 ◽  
Objective Response ◽  
High Dose ◽  
Cell Transplant ◽  
Synergistic Activity

TPS8051 Background: Multiple myeloma (MM) remains an incurable hematologic malignancy despite the advent of new classes of drugs, including immunomodulatory agents, proteasome inhibitors, and monoclonal antibodies. The success and synergistic activity of immunotherapy (IMT) in solid tumors and hematologic malignancies has fueled their investigation in MM. HDT/ASCT as consolidation or as treatment for relapse remains a cornerstone for improving overall survival. HDT/ASCT transiently eliminates immune-suppressive cell populations and provides a viable IMT platform. Reinfusion of PBLs harvested pre-HDT induces immune responses, supporting its inclusion in IMT combinations. This study evaluates the effect of IMT, using tremelimumab (T), an anti-CTLA-4 monoclonal antibody, and durvalumab (D), an anti-PD-L1 monoclonal antibody, together with autologous PBL reinfusion and starting T ± D at Day 100 and earlier (Day 30) post-ASCT. Methods: This ongoing Phase 1, open-label, multicenter study (NCT02716805) evaluates the safety and preliminary efficacy of T and D administered on 2 schedules in MM patients at high risk for relapse as outlined below. Cohort initiation requires dose-limiting toxicity in < 2/6 patients in the previous cohort. The primary endpoint is safety. Secondary endpoints are objective response rate per IMWG, minimal residual disease, progression free and overall survival, and 100-day ASCT-related mortality. Exploratory endpoints include immunological effects and immune response. Enrollment opened 18 Nov 2016. As of 31 Dec 2016, 1 patient is enrolled in Cohort 1; enrollment is ongoing. Clinical trial information: NCT02716805. [Table: see text]

scholarly journals A Phase 2 Multi-Center, Open Label Study of Isatuximab Added to Standard Cybord Induction and Lenalidomide Maintenance Treatments in Newly Diagnosed, Transplant Eligible Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4767-4767
Author(s):  
Rami Kotb ◽  
Engin Gul ◽  
Donna E. Reece
Keyword(s):  
Stem Cell ◽  
Sample Size ◽  
Research Funding ◽  
Response Rate ◽  
Autologous Stem Cell Transplant ◽  
Induction Treatment ◽  
High Dose ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
High Dose Melphalan

Abstract Background: Despite recent improvements, myeloma is still incurable. There is need to add new therapeutic tools. For young and fit patients, the current standard first-line therapy is a proteasome inhibitor (PI) containing induction, followed by stem cell collection, high dose Melphalan and autologous stem cell transplantation, followed by maintenance lenalidomide therapy in Canada. The anti-CD38 antibodies showed interesting activity in myeloma, and significant synergism with PI and IMiD based regimens. This CMRG-008 trial is designed to explore the benefit of adding Isatuximab to the current Canadian standard of care (CyBorD induction/Autologous SCT/Maintenance Len) in a single arm phase II trial. Design and Methods: Phase II study. Transplant eligible newly diagnosed myeloma patients (TE-NDMM) will receive Isatuximab added to four cycles of standard induction CyBorD chemotherapy (Cyclophosphamide 300 mg/m 2 PO, Bortezomib 1.5 mg/m 2 SC, and Dex 40 mg PO, all given on days 1, 8, 15 and 22 of 28-day cycles; Isatuximab 10 mg/kg IV days 1, 8, 15 and 22 of cycle 1; days 1 and 15 of cycles 2-4). After the completion of the induction treatment, subjects achieving at least stable disease will receive stem cell mobilization, collection of hematopoietic stem cells, high dose melphalan chemotherapy, and autologous stem cell transplantation. Maintenance treatment will start at 100 days (+/- 7 days) after the transplantation date (and to be continued until disease progression). The maintenance treatment will consist of Isatuximab administered in combination with Lenalidomide in 28-day cycles (Lenalidomide: 10 mg daily on days 1-21 of every cycle; Isatuximab: 10 mg/kg IV on days days 1, 8, 15 and 22 of cycle 1; days 1 & 15 of cycles 2-3; then day 1 of each subsequent cycle). The objectives: To evaluate the benefit of adding Isatuximab to CyBorD (induction = Isa + CyBorD) and Lenalidomide (maintenance = Isa + Lenalidomide) in transplant-eligible myeloma patients. Primary Endpoint: To determine the response rate (VGPR or better) defined by IMWG criteria at 100 days (+/- 7 days) after the autologous stem cell transplant (ASCT). Secondary Endpoints: A) To determine the response rate (VGPR or better) after induction treatment (before ASCT), and at 12 months, 24 months and 36 months. B) To evaluate additional efficacy outcomes including progression free survival (PFS), and overall survival (OS), time to response and duration of response. C) To confirm the feasibility, safety and tolerability of adding Isatuximab to CyBorD and to maintenance lenalidomide in transplant-eligible newly diagnosed myeloma patients. D) To determine the feasibility of autologous stem cell collection after Isa + CyBorD induction treatment. The key inclusion criteria are having a TE-NDMM with a measurable disease; adequate performance status; and adequate organ functions. The key exclusion criteria include previous exposure to anti-CD38 therapy, intolerance to CyBorD, adverse cardiac history, pulmonary disease, central nervous system disease, congenital or acquired immune suppression, and other concurrent severe or uncontrolled medical conditions. Statistics and Sample Size: Considering that the response rate (VGPR or better) after CyBorD induction therapy, high dose chemotherapy and autologous SCT is about 70-78%; and assuming a response rate (VGPR or better) to Isa-CyBorD induction and autologous stem cell transplant at 100 +/- 7 days of 88%; a sample size of 65 evaluable subjects will allow estimating the 95% confidence interval with a precision of +/- 7.9%. For the assumed rate and sample size, the lower bound of the confidence interval will be estimated to be larger than 80%. Assuming a 10% drop out rate, a total study size of 72 patients will be considered. This study is expected to open to recruitment in the third quarter of 2021. Clinicaltrials.gov #: NCT04786028. Disclosures Kotb: Janssen: Honoraria; Merck: Honoraria, Research Funding; Amgen: Honoraria; Akcea: Honoraria; Celgene: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria, Research Funding; Takeda: Honoraria; Karyopharm: Current holder of individual stocks in a privately-held company. Reece: BMS: Honoraria, Research Funding; GSK: Honoraria; Karyopharm: Consultancy, Research Funding; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Millennium: Research Funding; Sanofi: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding.

scholarly journals Clinical Characteristics, Treatment Regimens and Survival in Elderly Patients with AL Amyloidosis in a Tertiary Referral Center

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5447-5447
Author(s):  
Jose Acevedo ◽  
Gheorghe Doros ◽  
Raphael Szalat ◽  
John Mark Sloan ◽  
Shayna Sarosiek ◽  
...  
Keyword(s):  
Overall Survival ◽  
Elderly Patients ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Proteasome Inhibitors ◽  
Median Number ◽  
Stage Ii ◽  
High Dose ◽  
Al Amyloidosis ◽  
Treatment Regimens

Background AL amyloidosis is the most common form of systemic amyloidosis, characterized by an associated plasma cell dyscrasia leading to extracellular fibril deposition causing organ dysfunction. In these patients there is a fine balance between treatment toxicities and tolerability due to frailty and presence of multiorgan involvement. This balance is increasingly recognized in the elderly but treatment and outcomes have not been systematically studied, where co-morbidities and frailty may compound morbidity and mortality. Methods A retrospective analysis of all patients 70 years or older who were evaluated at the Boston University (BU) Amyloidosis Center from 2000 until 2018 was performed to determine demographics, clinical characteristics, treatments and outcome measures. Kaplan Meier method was used to perform an overall survival (OS) of all patients from the time of diagnosis. Further analysis of OS was performed based on whether treatment was received before or after 2010 (when proteasome inhibitors were incorporated in the treatment algorithm for AL amyloidosis), whether administered treatment regimens consisted of proteasome inhibitors (PI), and whether or not treatment with high dose melphalan and stem cell transplantation (HDM/SCT) was received. Results A total of 342 patients with AL amyloidosis who were older than 70 years of age at the time of diagnosis had their initial evaluation at BU Amyloidosis Center from 2000 to 2018. There were 215 (63%) men. The median age was 74 years (range, 70 - 90), and 55 (16%) were older than 80 years of age. The majority of patients were Caucasians (90%). The median number of organs involved by AL amyloidosis was 2 (range, 1- 7). The most common organ involvement was renal in 229 patients (68.3%), followed by cardiac in 167 patients (48.8%), and neurologic in 98 (29.2%). The majority of patients had renal stage II disease and BU cardiac stage II disease. Of the 342 patients, 223 (65%) received systemic treatment, the remainder (35%) received only supportive treatment. The median number of chemotherapy regimens administered was 1 (range 1-5), 116 patients (52%) received one regimen, 81 (36.1%) received two regimens, 35 (15.6%) patients received more than three treatment regimens. Of the 342 patients, 32 (9.4%) received treatment with HDM/SCT. The median age of patients undergoing HDM/SCT was 71 years (range, 70-75). The median overall survival was 3.4 years (95% CI 2.9-4.1) with a median follow-up of 2.6 years (range, 0.02-15.2). The median OS of patients treated with PI based therapy was 6.0 years vs 3.7 years for those not treated with PI based regimens (p=0.01) (Figure 1). The median OS of patients was 6.8 years for patients treated with HDM/SCT and 4.0 years for those not receiving HDM/SCT (p=0.08). Moreover, the median OS of patients diagnosed prior to 2010 was 3.4 years which is similar to 3.9 years for those diagnosed after 2010 (p=0.07). Conclusion In summary, the presentation of elderly patients with systemic AL amyloidosis is similar to that of younger patients in general. There are a higher proportion of patients with advanced cardiac and renal stage disease, perhaps reflecting delay in diagnosis. Compared to supportive care, overall survival in those receiving a PI based therapy is better with respect to survival, although this may reflect selection bias. In addition, HDM/SCT can be offered to highly selected patients with age older than 70 years. Prospective studies in older patients with novel agents with a better toxicity profile and ease of administration may allow a greater proportion of patients to benefit from treatment. Figure 1 Disclosures Sloan: Merck: Other: endpoint review commitee; Stemline: Consultancy; Abbvie: Other: Endpoint Review Committee. Sarosiek:Acrotech: Research Funding. Sanchorawala:Proclara: Consultancy, Honoraria; Caelum: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Prothena: Research Funding; Celgene: Research Funding; Takeda: Research Funding.

scholarly journals The Impact of 20q Deletion on Clinical Presentation, Treatment Response and Survival in Patients with Acute Myeloid Leukemia (AML): The University of Texas MD Anderson Cancer Center Experience

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1369-1369
Author(s):  
Jad Chahoud ◽  
Hagop M. Kantarjian ◽  
Farhad Ravandi ◽  
Koji Sasaki ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Response ◽  
Research Funding ◽  
Objective Response ◽  
Normal Karyotype ◽  
Prognostic Indicators ◽  
Cancer Center ◽  
Cytogenetic Abnormalities ◽  
Md Anderson ◽  
The Impact

Abstract Background: Karyotype classification is one of the strongest independent prognostic indicators in AML. The majority of recurring chromosomal aberrations are associated with an individual prognosis, other less frequent like the Del (20q), have been minimally evaluated and classified as intermediate risk in AML. Multiple studies established isolated 20q deletion as a good prognostic marker in MDS, with lower AML transformation rates and longer median overall survival (OS) in comparison with complex 20q deletion. Objective: The aim of this study is to determine the frequency and the impact on outcome of 20q deletion alone or with additional cytogenetic abnormalities in adult patients with AML. Patients and Methods: AML patients with chromosome 20 abnormalities were identified between 2000 and 2012 through the MD Anderson Cancer Center AML database (n=1741). Collected data included baseline demographics, number and type of additional cytogenetic abnormalities, disease characteristics, treatment and outcome. OS was defined as time from hematological diagnosis to death or last follow-up and relapse-free survival (RFS) was measured from time of hematological response to relapse. The Kaplan-Meier product limit method was used to estimate overall survival and the log-rank tests were employed for statistical comparisons between the OS curves. Results: From a total of 1741 adult AML patients, we identified 35 with Del (20q), representing 2% of our cohort. The distribution of cytogenetic abnormalities was as follows: isolated Del (20q) in 5 (14%), +8 in 3 (9%), +8 complex in 2 (6%), -5 complex in 8 (23%), -7 complex in 5 (14%), -7 not complex in 1 (3%), -5 and -7 complex in 6 (17%), other complex in 1 (3%), and other not complex in 4 (11%). Patients with Del (20q) were older (p=0.04), with lower bone marrow blast numbers (p<0.001), and lower WBC (p=0.001) compared to patients without Del (20q) (Table 1). Median RFS and OS for patients with Del (20q) were 16.8 and 7.5 months (mos), respectively. Objective response rates were 43% and 65% for patients with and without Del (20q), respectively (p=0.04) and the CR rates were 36% and 58%, respectively (p=0.01). Significant benefit was observed for OS in patients without Del (20q) (13.5 mos; 95% CI, 13.45-13.49; p=0.011), but not in RFS (19.52 mos; 95% CI, 19.48-19.55; p=0.376) in comparison with patients with Del (20q) (16.8 mos; 95% CI, 16.41-17.23; and 7.5 mos; 95% CI, 7.26-7.73). Patients with Del (20q) were compared to the remaining patients with leukemia classified as unfavorable cytogenetic status; the median survival for Del (20q) patients was similar by OS (OS 6.9 mos, 95% CI, 6.82-6.91). On the other hand, patients with Del (20q) had a significantly decreased overall survival (7.5 mos; 95% CI, 7.26-7.73, p=0.002) in comparison to patients with normal karyotype (17.7 mos; 95% CI, 17.64-17.71). No difference in survival was observed between patients with isolated Del (20q) and those with additional cytogenetic abnormalities: the median OS were 5 and 7.5 mos, respectively (p=0.964) (Figure 1). Conclusion: Our data demonstrated that Del (20q) occurs in 2% of previously untreated AML patients, with around 63% of these patients showing complex karyotype. Patients with Del (20q) have lower response rate and worse outcome, similar to patients with unfavorable cytogenetics. Table 1. Clinical descriptors, hematologic parameters and outcome of each set of patients Del 20qin Karyotype All othersnon-Del 20q P N = 35 N = 1706 Age (y), median (range) 65 (35-83) 61 (12-89) 0.04 Baseline hematologic data median (range) WBC × 109/L 2.7 (0.7-32.6) 5.8 (0.3-433) 0.001 Hemoglobin, g/dL 8.1 (5.6-14.2) 8.7 (2-93.3) 0.29 Platelet count, × 109/L 40 (7-254) 49 (2-676) 0.21 Neutrophil 29 (4-88) 16 (0-94) <0.001 PB blasts 9 (0-50) 16 (0-99) 0.02 BM blasts 30 (7-98) 47 (0-99) <0.001 Treatment Response and Survival Prior Chemo/XRT 7 301 0.72 CR 13 (37%) 990 (58%) 0.01 CRp 3 (9%) 88 (5%) 0.03 Cri 0 18 (1%) - RFS median, mo (95% CI) 17.22 (16.81-17.62) 25.59 (25.56-25-62) 0.55 OS median, mo (95% CI) 7.49 (7.26-7.73) 13.47 (13.45-13.49) 0.01 Disclosures Chahoud: American Society of Hematology (ASH): Other: 2015 HONORS Award recipient. Off Label Use: Inotuzumab.. Cortes:Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; BMS: Consultancy, Research Funding; BerGenBio AS: Research Funding; Teva: Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy.

Retrospective Comparison of Transplant Outcomes in Patients with Multiple Myeloma According to Induction Therapy with Thalidomide/Dexamethasone (TD) with or without Bortezomib (VTD).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 948-948 ◽  
Author(s):  
Sergio Giralt ◽  
Rupi Thandi ◽  
Muzaffar Qazilbash ◽  
Floralyn Mendoza ◽  
Eric Han ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Therapy ◽  
Response Rates ◽  
Induction Treatment ◽  
High Dose ◽  
Cell Transplant ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Treatment Characteristics ◽  
The Impact

Abstract Background: Thalidomide/Dexamethasone (TD) has become one of the most commonly used induction therapies for patients with symptomatic multiple myeloma (MM) eligible for high dose therapy (HDT) intensification with autologous stem cell transplant (ASCT). Bortezomib (Velcade) has been added to the combination of TD (VTD) in an effort to reduce MM tumor burden further prior to HDT.The impact of this addition on HDT outcomes has not been fully explored. Purpose: To determine the impact of the addition of bortezomib to TD induction therapy in patients with MM undergoing HDT and ASCT consolidation. Patients and Methods: Patients were eligible for this analysis if they had undergone HDT with ASCT for first remission consolidation or primary refractory disease within 12 months of diagnosis between 9/03 and 12/05 and had received either TD or VTD as induction therapy. Patients receiving VTD after TD were excluded. Patients receiving more than 1 chemo regimen other than TD or VTD were excluded. Chemomobilization was NOT considered an exclusion criteria. Results A total of 78 patients qualified for the analysis (27 VTD; 51 TD). Patient and treatment characteristics are summarized in table 1. In brief, the patients receiving VTD had a higher rate of cytogenetic abnormalities and received less cycles of chemotherapy prior to SCT. Although pre-SCT response rates were similar between patients receiving VTD or TD (95% vs 92%) there was a trend for a higher CR rate in the VTD group (15% vs 6%). Post transplants response rates assessed between 3–6 months demonstrated that 28% and 38% of VTD patients achieved near CR and CR respectively while 19% and 23% had these responses post TD induction. There was no difference in 2 year OS and PFS among patients receiving VTD or TD (91% vs 81% and 35% and 56% respectively). Conclusion: Both VTD and TD as induction treatment are associated with high response rates prior to SCT as well as 6 months post SCT. In this retrospective analysis no survival benefit was seen for induction therapy with VTD over TD, despite higher near CR and CR rates. However randomized trials need to be performed addressing type of induction as well as duration of induction therapy prior to high dose therapy consolidation. Patient and Treatment Characteristics Variables VTD TD N 27 51 Median Age 54 (34–71) 56 (34–71) %ISS> 1 76% 65% % CG Abnormal 37% 19% p=.009 B2M @ Dx 2.99 3.19 Cycles Prior to SCT 2 4 p=.00009 % Mel 200 74% 69% Post SCT Maintenance 15/27 23/51

European MCL Network: An Update on Current First Line Trials.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 388-388 ◽  
Author(s):  
Martin H. Dreyling ◽  
Eva Hoster ◽  
Olivier Hermine ◽  
J.C. Kluin-Nelemans ◽  
Jan Walewski ◽  
...  
Keyword(s):  
Overall Survival ◽  
Febrile Neutropenia ◽  
Elderly Patients ◽  
Response Rate ◽  
Response Rates ◽  
High Dose ◽  
High Dose Cytarabine ◽  
The Impact ◽  
Grade Iii

Abstract Background: Conventional chemotherapy achieves only short term remission despite high initial response rates of 70%–80%. In the current study generation, the European MCL Network investigates the impact of various combined immuno-chemotherapy regimens. Additionally, in elderly patients the role of rituximab maintenance is being evaluated, whereas in younger patients dose-intensified regimens with implementation of high dose cytarabine are investigated based on the excellent results of the HyperCVAD regimen. Methods: In MCL elderly, patients are initially randomized between 8 cycles of R-CHOP or 6 cycles of R-FC (experimental arm). Patients who achieve either an PR or CR, receive subsequently either interferon maintenance (standard arm) or a single rituximab dose every 2 months. In MCL younger, the standard arm (R-CHOP induction followed by myeloablative consolidation: 12 Gray TBI, 2x 60mg/kg cyclophosphamide) is compared to the implementation of high dose cytarabine into induction (R-CHOP/R-DHAP) and consolidation (10 Gray TBI, 4x1,5 g/m2 Ara-C, 140mg/m2 melphalan). Results: In MCL elderly, 222 of 263 patients were evaluable based on the annual interim analysis. Median age was 70 years with 66% of patients displaying an intermediate high/high risk IPI. Induction was well tolerated with mainly hematological toxicity (grade III/IV in R-CHOP/R-FC): Leukocytopenia 62/72%, thrombocytopenia 13%/40%, but only rare febrile neutropenia (23%/7%) or infections (19%/23%). Despite the poor risk profile, combined immuno-chemotherapy (total group) achieved a remarkable 84% response rate (51% CR/CRu). Although the impact of maintenance is not yet evaluable, both progression-free and overall survival were encouraging with 77% and 86% at 12 months, respectively. In MCL younger, 247 of 271 patients were evaluable. Again, toxicity (grade III/IV in R-CHOP/alternating R-DHAP) was mainly hematological: leukocytopenia 58/77%, thrombocytopenia 14%/74%, but only rare febrile neutropenia (11%/22%) or infections (5%/7%). Combined immuno-chemotherapy achieved a 93% response rate (60% CR/CRu) before subsequent high dose consolidation. Again, both progression-free and overall survival are remarkable with both 90% at 12 months, respectively. Discussion: Combined immuno-chemotherapy results in high response rates in two prospective international trials. Further recruitment and follow-up will determine the role of rituximab maintenance and high dose cytarabine in this distinct subtype of malignant lymphoma.

Vinorelbine, Paclitaxel, Etoposide, Cisplatin and Cytarabine (VTEPA) Is An Effective Salvage Therapy for Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) but Not for R/R Diffuse Large B Cell Lymphoma (DLBCL)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1628-1628 ◽  
Author(s):  
Rajni Sinha ◽  
Nassoma King ◽  
Pareen J Shenoy ◽  
Mary Jo Lechowicz ◽  
Kevin Bumpers ◽  
...  
Keyword(s):  
Stem Cell ◽  
Salvage Therapy ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
Electrolyte Imbalance ◽  
Stage Iii ◽  
High Dose ◽  
Cell Transplant ◽  
Refractory Disease ◽  
Relapsed Disease

Abstract Abstract 1628 Introduction: Historically, relapsed DLBCL and HL has been associated with a high cure rate with salvage regimens followed by high dose chemotherapy and stem cell transplant (ASCT). However, patients (pts) who relapse early following upfront chemotherapy and pts who fail to respond to salvage have a poor overall response rate (ORR) with additional salvage regimens and a poor prognosis even when consolidated with ASCT (von Tresckow & Engert, 2011; Gisselbrecht et al., 2010). At present there is no standard therapy in the third-line setting for pts with DLBCL and HL. We designed a regimen: vinorelbine (30mg/m2) & paclitaxel (175mg/m2) given on day 1; etoposide (100mg/m2) & cisplatin (20mg/m2) given on days 2–5; and cytarabine (2000mg/m2) on days 4 and 5 (VTEPA) for treatment of lymphoma pts with 1° refractory disease or relapse following salvage. In phase 1, VTEPA was safe with a 33% ORR following 1 cycle (Lonial et al, 2006). Design and Methods: To examine the effectiveness of VTEPA, we conducted an IRB approved retrospective review of consecutive cases of relapsed/refractory DLBCL and HL identified from our database from 1999–2011. All pts had evidence of primary refractory disease or stable or progressive disease following first line salvage therapy. Responses following salvage VTEPA were retrospectively assessed using International Working Group Criteria (JCO 1999) for all pts. Responding pts proceeded to ASCT. Survival curves were constructed using the Kaplan-Meier method and compared with the log-rank test. Results: 74 pts (44 DLBCL and 30 HL) with a median age at diagnosis of 30 years (range 18–63) for HL and 49 years (range 20–68) for DLBCL were included. 67% of HL pts had primary refractory disease and 33% of pts had relapsed disease; 60% were stage III/IV at diagnosis. 75% of DLBCL pts had primary refractory disease and 25% of pts had relapsed disease; 73% stage III/IV. Pts received a median of 2 prior therapies (range 1–4). 63% pts with HL received prior salvage therapy with ifosfamide, carboplatin, and etoposide (ICE) and 13% with other regimens. 16 pts with HL received 1 cycle of VTEPA, 13 received 2 cycles and 1 pt received 3 cycles of VTEPA. 70% pts with DLBCL had received prior salvage therapy with rituximab (R) + ICE and 16% received other salvage regimens. 32 pts with DLBCL received 1 cycle of R-VTEPA and 12 pts received 2 cycles. The most common reported grade 3/4 toxicities were pancytopenia (97%), nausea/vomiting (58%), fatigue (30%), infectious complications (26%), diarrhea (24%), electrolyte imbalance (19%), and mucositis (16%). 70 pts (43 DLBCL and 27 HL) were evaluable for response. The ORR for DLBCL pts was 44% (9% CR and 35% PR) while that for HL pts was 70% (26% CR and 44% PR, p=0.04). 4 DLBCL pts had treatment related mortality. 34 pts went on to collect ≥2 × 106 CD34+ cells/kg; 3 pts had inadequate stem cell collection. In 23 pts collection was not attempted, and 14 pts collected stem cells prior to R+/−VTEPA. 37 pts (47%) went onto planned ASCT, and 4 pts underwent allogeneic transplantation. The PFS at 2 years for pts with HL was 68% vs. 49% for pts with DLBCL (p<0.001, Figure 1). Similarly the OS at 2 years for pts with HL was 79% vs. 41% for pts with DLBCL (p<0.001, Figure 2). Conclusions: Treatment with VTEPA for heavily pretreated relapsed/refractory HL and DLBCL pts is feasible with manageable side effects, a high ORR, and permits transplantation for nearly ½ of pts. Nevertheless, outcomes for pts with refractory DLBCL is exceedingly poor compared to refractory pts with HL treated with the same approach. While there remains a great need for novel agents to aid DLBCL pts who are chemotherapy and R refractory, the favorable PFS and OS for relapsed/refractory HL pts suggest VTEPA is a promising salvage regimen for this disease. Disclosures: Sinha: Celgene: Research Funding. Kaufman:Millenium; Onxy; Novartis; Keryx: Research Funding; Merk, Celgene: Research Funding. Flowers:Spectrum: Consultancy, Research Funding; Millennium/Takeda: Research Funding; Celgene: Consultancy; Genentech/Roche (unpaid): Consultancy; Novartis: Research Funding; Seattle Genetics: Consultancy.

Lenalidomide Related Diarrhea Correlates With Survival In Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5397-5397 ◽  
Author(s):  
Beth Faiman ◽  
Surbhi Sidana ◽  
Paul Elson ◽  
Kellie Bruening ◽  
Hien K. Duong ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Antineoplastic Agents ◽  
Research Funding ◽  
Proportional Hazards ◽  
Late Onset ◽  
High Dose ◽  
Cell Transplant ◽  
Logrank Test ◽  
The Impact

Abstract Background We hypothesized lenalidomide (len) related diarrhea (LRD) may correlate with activation of an immune response against multiple myeloma (MM) based on colon biopsies that showed crypt apoptosis reminiscent of GVHD in 3 MM patients with severe LRD but without prior allogeneic stem cell transplantation or gastrointestinal disorder. To investigate whether survival may be influenced by the presence of LRD we performed a retrospective chart review. Methods Patients who developed symptomatic MM on or after 1/1/2005 as defined by the start of anti-MM therapy and had been on len for at least 6 consecutive months by 12/31/2010 were included in the analysis. Significant LRD was considered present if the treating physician attributed the diarrhea to len and recommended supportive therapy in at least two clinic notes.  The first time treatment for LRD was recommended was used as the date of onset of LRD. As possible confounding factors age at the start of len therapy, number of prior regimens, prior high dose chemotherapy with autologous stem cell transplant (ASCT), and use of antineoplastic agents other than corticosteroids at any time during the continuous len therapy were collected. The primary outcome was overall survival (OS), which was calculated from the start of len. Fisher’s exact test, Mann-Whitney test, and the logrank test were used to compare characteristics and duration of len between patients with and without LRD. Proportional hazards models were used to assess the impact of LRD on OS. The lag between the start of len and development of LRD was accounted for by treating LRD as a time-varying covariate in these models. Results 161 patients were identified, 47 (29%) had LRD, and 59 (37%) died during follow up. LRD and no LRD groups were balanced for gender, age, number of prior regimens, prior transplant, and use of antineoplastic agents other than corticosteroids with len, but len treatment duration differed; LRD patients had received a median of  43.4 consecutive months of len (range 5.8-82.9) compared to 14.6 (range 5.9-89) for patients without LRD (p=0.001). Onset of LRD occurred after a median of 17.7 months (range 0.3-75.4) of len therapy. In multivariable analyses, development of LRD (HR 0.46, 95% C.I. 0.21-1.00, p=0.05) was associated with improved OS as were the number of prior therapies (0-2, vs >2, HR 0.16, 95% C.I. 0.08-0.32, p<0.0001) and no use of antineoplastic therapy other than corticosteroids during len therapy (HR 0.52, 95% C.I. 0.29-0.93, p=0.03), while age and prior ASCT (p=0.52 and 0.49, respectively) were not. Conclusion Late onset of lenalidomide related diarrhea (LRD) is compatible with an immune mediated effect that may signal anti-MM immune activity since LRD requiring supportive measures correlated with survival in MM in analyses that adjusted for lag time. While more study is needed to prove this hypothesis, our findings suggest that diarrhea on len may argue for continued therapy rather than discontinuation. Disclosures: Faiman: Celgene: Consultancy, Speakers Bureau; Millennium: Consultancy, Speakers Bureau; Onyx: Consultancy, Speakers Bureau. Duong:Celgene: Honoraria, Research Funding. Valent:Celgene: Speakers Bureau; Millennium: Speakers Bureau. Reu:Celgene: Research Funding; Onyx: Speakers Bureau.

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