Similar Outcomes among African-Americans (AA) and Whites after Autologous Hematopoietic-Cell Transplantation (Auto HCT) for Multiple Myeloma (MM)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 740-740 ◽  
Author(s):  
Parameswaran Hari ◽  
Navneet S. Majhail ◽  
Anna Hassebroek ◽  
Mei-Jie Zhang ◽  
Fareeha Siddiqui ◽  
...  
Keyword(s):  
Overall Survival ◽  
Renal Function ◽  
African Americans ◽  
Progression Free Survival ◽  
Free Survival ◽  
Post Transplant ◽  
Transplant Outcomes ◽  
Remission Status ◽  
Response To Chemotherapy ◽  
White Patients

Abstract MM is the most common hematological malignancy among AA adults and AA have twice the incidence and mortality from MM compared to Whites (SEER data, 2007). Based on CIBMTR registration rates of Auto HCT and incidence rates for MM, AA patients have been shown to have significantly lower likelihood of receiving Auto HCT (age adjusted odds ratio 0.58) compared to White patients with MM. The characteristics of AA patients who undergo Auto HCT for MM and their post transplant outcomes have not been compared to that of White MM patients. We compared characteristics and post-transplant outcomes of AA (N=303) and White (N=1892) patients receiving a first Auto HCT for MM and reporting to the CIBMTR between 1995 and 2005. Recipients of tandem Auto HCT were excluded. Compared to Whites, AA were significantly younger (29% aged <50 yr vs 21%, p=0.002), had better performance status at Auto HCT (69% with KPS score ≥90 vs 61%, p=0.005) and had higher incidence of hypertension (47% vs 25%, p<0.001), diabetes mellitus (17 % vs 9%, p<0.001) and morbid obesity (38% vs 31%, p=0.01). Durie-Salmon stage, immunoglobulin subtype, renal function, number of prior chemotherapy regimens, response to chemotherapy and remission status at transplant were similar in both groups. Transplant was more likely to be performed later (>12 months from diagnosis) in AA (37% vs 28% in Whites, p<0.001). The proportion of AA receiving Auto HCT increased from 7% in 1995 to 17% in 2004. No significant differences were found between AA and Whites in overall survival (52% vs 47%, at 5 years), progression-free survival (19% vs 21%, at 5 years), non-relapse mortality (3% vs 5%, at 1 year), or relapse (72% at 5 years in both groups) after Auto HCT. In multivariate analyses adjusting for patient, disease and transplant-related variables, race did not impact overall survival, progression-free survival, non-relapse mortality, or relapse (Table 1). We conclude that despite increased pre-transplant co-morbidities and transplantation later in the course of disease, post-transplant outcomes are comparable among AA and White patients who undergo Auto HCT for MM. The lower transplant rates in AA and the differences in pre-transplant patient characteristics need further investigation to explore racial differences in patient referral and selection for Auto HCT. Table 1: Multivariate analysis: African-Americans vs. Whites (reference group) Outcome Relative Risk 95% CI P-value Overall survival 0.94 0.78–1.13 0.50 Progression-free survival 0.94 0.81–1.09 0.42 Non-relapse mortality 1.16 0.75–1.80 0.51 Relapse 0.92 0.78–1.08 0.31 Adjusted for age, gender, KPS score at transplant, comorbidities (hypertension, diabetes, obesity, smoking), renal function, immunoglobulin subtype, Durie-Salmon stage, number of previous chemotherapy regimens, response to chemotherapy, remission status, time since diagnosis and year of transplant

Progression-Free Survival in Children With Optic Pathway Tumors: Dependence on Age and the Quality of the Response to Chemotherapy—Results of the First French Prospective Study for the French Society of Pediatric Oncology

2003 ◽  
Vol 21 (24) ◽  
pp. 4572-4578 ◽  
Author(s):  
Véronique Laithier ◽  
Jacques Grill ◽  
Marie-Cécile Le Deley ◽  
Marie-Madeleine Ruchoux ◽  
Dominique Couanet ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Disease Progression ◽  
Objective Response ◽  
Progression Free Survival ◽  
Optic Pathway ◽  
Free Survival ◽  
Factors Associated ◽  
Response To Chemotherapy ◽  
Risk Of Disease

Purpose: To evaluate a strategy aimed at avoiding radiotherapy during first-line treatment of children with progressive optic pathway tumors (OPT), by exclusively administering multiagent chemotherapy during 16 months. Patients and Methods: Between 1990 and 1998, 85 children with progressive OPT were enrolled onto this multicenter nationwide trial. Chemotherapy alternating procarbazine plus carboplatin, etoposide plus cisplatin, and vincristine plus cyclophosphamide was given every 3 weeks. At the time of relapse or progression, second-line chemotherapy was authorized before recourse to radiotherapy. Results: Objective response rate (partial response [PR] + complete response [CR]) to chemotherapy was 42%. Five-year progression-free survival (PFS) and overall survival rates were 34% and 89%, respectively. The 5-year radiotherapy-free survival rate was 61%. In the multivariate analysis of the 85 patients that entered onto the study, factors associated with the risk of disease progression were age younger than 1 year at diagnosis (P = .047) and absence of neurofibromatosis type 1 (P = .035). In the multivariate analysis of the 74 patients that remained on study after the first cycle of chemotherapy, factors associated with the risk of disease progression were age younger than 1 year at diagnosis (P = .0053) and no objective response to chemotherapy (P = .0029). Three-year PFS was 44% in infants ≤ 1 year versus 66% in children older than 1 year. Three-year PFS was 53% in the absence of an objective response to chemotherapy versus 68% after a PR or CR. Conclusion: A significant proportion of children with OPT can avoid radiotherapy after prolonged chemotherapy. Deferring irradiation with chemotherapy protocols did not compromise overall survival of the entire population or visual function.

Total Body Irradiation, Etoposide, Cyclophosphamide and Autologous Peripheral Blood Stem Cell Transplantation Followed by Randomization to Therapy with Interleukin-2 Versus Observation for Patients with Non-Hodgkin’s Lymphoma: Results of a Phase III Randomized Trial by the Southwest Oncology Group (SWOG 9438).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 326-326 ◽  
Author(s):  
John A. Thompson ◽  
Richard I. Fisher ◽  
Michael L. LeBlanc ◽  
Joseph M. Unger ◽  
Stephen J. Forman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Peripheral Blood Stem Cell ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
High Grade ◽  
Survival Estimate ◽  
Free Survival ◽  
Post Transplant ◽  
Total Body

Abstract Purpose: To determine the effect of post-transplant immunotherapy with Interleukin-2 (IL-2) on the progression-free and overall survival of patients with non-Hodgkin’s lymphoma (NHL) after autologous stem cell transplantation and to assess the toxicity of post-transplant IL-2 therapy. Patients and Methods: Patients with previously treated low, intermediate, or high grade NHL (except Working Formulation Groups A and I) were treated with high-dose cyclophosphamide, etoposide, and total body irradiation (TBI) and an autologous peripheral blood stem cell transplant (PBSCT). Twenty-eight to 80 days after PBSCT, patients were randomized to treatment with IL-2 versus observation. Results: Between January 1995 and July 2004, three hundred ninety-four patients with low-grade (n=61) or intermediate-high grade NHL (n=315) were registered at one of 39 SWOG transplant centers. One hundred ninety patients did not proceed to randomization, because of patient refusal (44), grade V toxicity (30), disease progression (28), toxicity (28), or other reasons. Two hundred four patients were randomized to treatment with continuous infusion intravenous IL-2 (9 ×106 units/m2/day for four days followed five days later by 1.6 ×106 units/m2/day for 10 days) versus observation. The 4-year progression-free survival estimate for all eligible patients is 34%, and the 4-year overall survival estimate is 52%. There was no difference in progression-free survival (hazard ratio (HR) of IL-2 to observation = 0.90; p = 0.56) nor in overall survival (HR of IL-2 to observation = 0.88; p = 0.55). There were no deaths related to IL-2 treatment. Grade IV IL-2-related toxicities included hematologic (n=10), cardiovascular (4), renal/bladder (2), flu-like symptoms (1), lung (1), metabolic (1), and neurologic (1) and were reversible in all cases. Conclusions: These results confirm earlier SWOG findings that a regimen of cylophosphamide, etoposide and TBI followed by PBSCT can be administered to patients with relapsed or refractory NHL with acceptable toxicity and with encouraging progression-free and overall survival. Post-transplant therapy with IL-2 given at this dose and schedule of administration had no significant effect on post-transplant relapse, progression-free survival or overall survival.

scholarly journals Autologous Haematopoietic Stem Cell Transplantation in Waldenström Macroglobulinemia: A Single-Centre 18-Year Experience

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3548-3548
Author(s):  
Suzanne O Arulogun ◽  
Charalampia Kyriakou ◽  
Jackie Horder ◽  
Fiona Newrick ◽  
Aisha S Patel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Partial Response ◽  
Research Funding ◽  
Progression Free Survival ◽  
Survival Outcomes ◽  
Free Survival ◽  
Depth Of Response ◽  
Remission Status

Abstract BACKGROUND The role of autologous stem cell transplantation (ASCT) in Waldenström Macroglobulinaemia (WM) is not well established, largely due to the paucity of evidence. It remains unclear where ASCT should be placed in the sequence of treatment lines. The debate is stronger in the era of targeted therapies that can achieve prolonged progression free survival (PFS) intervals and expected treatment-free intervals of approximately 4 to 8 years. The goal of this real world analysis was to review response and survival outcomes, and relapse risk factors in WM patients who underwent ASCT in a single WM referral centre. METHODS A retrospective cohort analysis was undertaken of consecutive WM patients treated with ASCT at a single specialist centre between 2003 and 2020. Baseline demographic/biological data, number/types of prior therapies, and pre- and post-ASCT depth of response, were collected from patient records and the WMUK Rory Morrison Registry. The primary aims were to determine depth of response, overall survival (OS), progression free survival (PFS), transplant related mortality (TRM) and relapse-associated mortality. RESULTS A total of 32 patients received ASCT, with a median age at time of ASCT of 57 years (range 40-68 years) and median interval from diagnosis to ASCT of 2.3 years (range 0.5-16.8 years); 14 (43.7%) were male. Prior to ASCT, 11 patients (34%) had received one therapy, 11 patients had 2 lines of treatment (excluding mobilisation), and 10 patients (31%) had received 3 or more therapies. The disease status pre-ASCT was complete remission (CR)/very good partial response (VGPR) in 14 patients (43.7%) and partial response (PR) in 18 patients (56.2%). Conditioning therapy comprised LEAM (Lomustine, Etoposide, Cytarabine, Melphalan; 18 patients, 56.2%), BEAM (Carmustine substituted for Lomustine; 12 patients, 37.5%), or Melphalan only (2, 6.2%). All patients had successful engraftment. Median time from stem cell reinfusion to hospital discharge was 15.5 days (range 13-187 days) in the 24 patients for whom these data were available; 5/24 patients (21%) were discharged &gt;25 days after stem cell reinfusion. Restaging at 100 days post-ASCT showed deepening of response by ASCT in 17 patients (53.1%). CR/VGPR was achieved by 26 patients (81.2%) and PR by 4 patients (12.5%). Two patients (6.2%) experienced disease progression before day 100 post-ASCT (both receiving ASCT in second remission/PR2). At a median follow up of 8.9 years (range 0.1-18 years), the estimated median PFS was 4.5 years (95% confidence interval [CI] 3.2-5.7 years), with estimated 2-year and 5-year PFS rates of 75% and 35.9%, respectively (Figure 1A). In this small cohort, there was no significant difference in PFS based on age, number of prior lines of treatment, pre-ASCT remission status (CR/VGPR vs PR) or post-ASCT response achieved. At time of analysis, 14/32 patients (43.7%) had died: TRM rate was 6.2% (2 patients died during inpatient admission of ASCT complications), 4 patients (12.5%) died of PD, and 1 patient died of unknown causes. Another 7 patients (21.9%) died of infective causes after the immediate post-ASCT period: the median time from ASCT to death among these patients was 5.5 years (range 0.8-10.8 years). Estimated median OS for the unstratified cohort was 10.8 years (95% CI 7.3-14.3 years), with estimated 2- and 5-year OS rates of 87.5% and 77.5%, respectively (Figure 1B). Overall survival did not differ significantly based on age at time of ASCT, number of therapy lines prior to ASCT, pre-ASCT remission status (CR/VGPR vs PR) or post-ASCT response achieved. One patient (3.1%) underwent ASCT after BTK inhibitor therapy, achieving deepening of response (PR to VGPR) with ASCT and progression free interval of 11 months. CONCLUSION ASCT is a feasible treatment option for patients with relapsed WM, producing deeper responses following salvage therapy and resulting in PFS intervals comparable to other currently available therapeutic options. With the benefit of a long follow up period, performing ASCT at later stages in the treatment course (i.e. following 3 or more prior therapy lines) did not appear to result in inferior survival outcomes; timing of ASCT should therefore be considered on an individual patient basis and in light of other available therapy options for relapsed disease. Figure 1 Figure 1. Disclosures Yong: Sanofi: Honoraria, Research Funding; GSK: Honoraria; Amgen: Honoraria; Autolus: Research Funding; BMS: Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria. Wechalekar: Amgen: Research Funding; Alexion, AstraZeneca Rare Disease: Consultancy; Caelum Biosciences: Other: Clinical Trial Funding; Takeda: Honoraria; Celgene: Honoraria; Janssen: Consultancy. D'Sa: Sanofi: Honoraria; Janssen Cilag: Honoraria, Research Funding; BeiGene: Honoraria, Research Funding.

scholarly journals Does Renal Failure Affect Outcome after Autologous Stem Cell Transplantation in Patients with Multiple Myeloma?

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4642-4642 ◽  
Author(s):  
Marlies Antlanger ◽  
Thomas Reiter ◽  
Wolfgang Lamm ◽  
Werner Rabitsch ◽  
Heinz Gisslinger ◽  
...  
Keyword(s):  
Overall Survival ◽  
Renal Failure ◽  
Renal Function ◽  
Renal Impairment ◽  
Board Of Directors ◽  
Impaired Renal Function ◽  
Progression Free Survival ◽  
Outcome Data ◽  
Advisory Committees ◽  
Free Survival

Abstract Introduction: Renal impairment (RI) is frequent in patients with Multiple Myeloma (MM) and is a proven negative prognostic factor for overall survival (OS). MM patients with impaired renal function often fail to qualify for high-dose chemotherapy and are excluded from autologous stem cell transplantation (ASCT), since a higher transplant-related mortality has been postulated. However, it remains unclear whether these historical inferior outcome data still hold true in times of modern immuno-chemotherapeutical therapy regimen. Further, nephrologic definition criteria for renal impairment have evolved as well and have not yet been fully introduced into MM patient care. We thus aimed at evaluating outcome data of MM patients undergoing ASCT after immuno-chemotherapy applying current nephrologic standard criteria for RI. Methods: MM patients who had undergone ASCT at our center between 1999 and 2015 were included. Renal function was determined and staged both at the time of diagnosis and transplantation by estimated glomerular filtration rate (eGFR according to the MDRD formula).RI was defined as eGFR <90 ml/min/m2. For sub-analyses renal failure was further staged according to KDIGO guidelines (CKD stages II, IIIa and IIIb corresponding to an eGFR of <60, <45 and <30 ml/min/m2). Kaplan-Meier curves and log-rank tests were used for OS and progression-free survival (PFS) calculation. Results: 195 patients with a median age of 54 years were analyzed. Patients were categorized into 3 groups: i) normal renal function at diagnosis and ASCT ii) impaired renal function at diagnosis with normalization before ASCT and iii) impaired renal function both at the time of diagnosis and ASCT. Estimated mean OS from diagnosis was 93 months (90% CI: 77-109). No difference in OS was found comparing these 3 groups (Figure 1). Estimated mean PFS was 83 months (90% CI: 12-61). Again, in our patient cohort, renal impairment did not negatively impact PFS (Figure 2). In addition, even after further stratification according to the degree of renal failure at the time of ASCT (CKD stage II, IIIa and IIIb), no survival disadvantage was detected for patients with mild to moderate renal failure. Conclusions: In this retrospective analysis, a relatively large cohort of MM patients who had undergone ASCT was analyzed regarding survival data in accordance with their renal function. Since RI is associated with poorer outcome in MM patients, we aimed at working out if this holds true for patients receiving ASCT. In contrast to historical data, our data show that neither OS nor PFS were negatively impacted by mild to moderate RI. Therefore, we conclude that ASCT should rather be considered proactively in MM patients with RI than be withheld, since survival in theses patients seems not to be affected in an adverse manner. Figure 1 Overall survival according to renal function groups. Figure 1. Overall survival according to renal function groups. Figure 2 Progression-free survival according to renal function groups. Figure 2. Progression-free survival according to renal function groups. Disclosures Agis: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

Rituximab Purging and Maintenance Improves Progression Free Survival but Not Overall Survival In Patients with Relapsed or Resistant Follicular Lymphoma Prior Receiving An Autologous Transplant

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3567-3567 ◽  
Author(s):  
Ruth Pettengell ◽  
Norbert Schmitz ◽  
Christian Gisselbrecht ◽  
Graeme Smith ◽  
William N Patton ◽  
...  
Keyword(s):  
Overall Survival ◽  
Peripheral Blood ◽  
Research Funding ◽  
Progression Free Survival ◽  
Phase Ii Trials ◽  
Free Survival ◽  
Post Transplant ◽  
Autologous Transplant

Abstract Abstract 3567 Autologous transplantation significantly improves the progression free survival (PFS) and overall survival (OS) of patients with relapsed or resistant follicular (rFL) lymphoma compared with chemotherapy alone (Schouten H, et al. J Clin Oncol 2003;21:3918–27). Small phase II trials suggest, that rituximab (R) given peritransplant further improves survival outcome. Whilst the role of maintenance R post chemotherapy in FL is established, the benefit and safety of maintenance R following autologous transplant is unknown. In this randomised prospective study the efficacy and safety of R as in vivo purging pretransplant and as maintenance treatment immediately post transplant was assessed. From Oct 1999 to Apr 2006, 280 of a planned 420 R naïve patients with rFL in first (n=16), second (n= 222) or third remission (n=41) who achieved either a complete remission (n=83) or a very good partial remission (n=196) to induction chemotherapy, with limited bone marrow infiltration (<25% B-lymphocytes) underwent a single randomisation in a 2 × 2 design to R purging 375 mg/m2 weekly × 4 (RP) before high-dose therapy with BEAM conditioning (HDC) and maintenance R 375 mg/m2 every 3 months for 2 years (RM). The primary endpoint of the study was PFS. All analysis is by intention to treat. The median age was 51 years (range: 26–70), and baseline characteristics were well balanced between groups. On average patients were 44.1 (range 3.4–463.8) months from diagnosis with 79.3% having 2 lines of therapy and 15% three lines of prior therapy. Patients were equally distributed between low, intermediate and high FLIPI scores. Pretransplant 70% of patients were in PR and 30% in CR. Fifty seven patients failed to mobilise peripheral blood stem cells. Nineteen patients withdrew, 5 due to toxicity, 9 were ineligible. In the 196 (70%) patients transplanted, neutrophil engraftment > 0.5 × 109 /L was prompt, median 14.3 days (range 10–115) and platelets > 50 × 109/L,median 25.1 days (range 9–190). Time to engraftment and early or late toxicities did not differ significantly between the groups apart from a lower neutrophil count at 3 months in patients on maintenance. No graft failures or late neutropenia was reported. Transplant related mortality was 0.5%. Only 3 infection related deaths have been reported post 100 days. Two hundred and seventeen patients are alive on continued follow-up. Median follow-up is 6.4 years. PFS at 5 years was 62.9% for patients receiving RP + RM versus 37.6 % for patients receiving no R (logrank PFS; p=0.004; HR 0.76, 95%CI: 0.66 – 0.93). OS at 5 years was 79.5% % versus 78.4 % for patient receiving RP + RM versus no R (logrank PFS; p>0.1). Multivariate analysis was not able to define a high or low risk patient group. R in vivo purging and maintenance results in superior PFS compared to no R. R does not adversely affect peripheral blood stem cell harvesting or engraftment and maintenance R post transplant is safe. The impressive OS suggests that relapsed FL patients can be effectively salvaged post R purging and maintenance. R Purging + R Maintenance R Maintenance R Purging No R Pt number 69 69 72 70 Median PFS NR@ 6.4 y 7.23 y 4.03 y 3.34 y 5y PFS 62.9 % 56 % 46 % 37.6 % 5y OS 79.5 % 80.5 % 84.8 % 78.4 % Disclosures: Pettengell: Roche: Honoraria. Schmitz:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Gisselbrecht:Roche: Research Funding. Walewski:Roche: Honoraria, Research Funding. Geisler:Roche: Research Funding. Kimby:Roche: Honoraria, Research Funding. Goldstone:Roche: Honoraria, Speakers Bureau.

A Phase I/II Study of the Tolerability of Lenalidomide and Low Dose Dexamethasone in Previously Treated Multiple Myeloma Patients with Impaired Renal Function: Pre1003, a Precog LLC Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1856-1856
Author(s):  
Joseph R. Mikhael ◽  
Judith Manola ◽  
Amylou Constance Dueck ◽  
Suzanne R Hayman ◽  
Kurt Oettel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Renal Function ◽  
Renal Insufficiency ◽  
Impaired Renal Function ◽  
Response Rate ◽  
Progression Free Survival ◽  
Free Survival ◽  
Previously Treated ◽  
Grade 3

Abstract Abstract 1856 Background: Lenalidomide has proven to be a highly effective treatment in relapsed multiple myeloma (MM), particularly when used in combination with dexamethasone. However, over 30% of patients with myeloma have renal insufficiency and as lenalidomide is renally excreted, little information is available about its use in myeloma patients with impaired kidney function. Defining a safe and effective dose of lenalidomide in this context is critical. Objective: We undertook this study to establish the maximum tolerated dose of lenalidomide in three cohorts of patients with different levels of impaired renal function: Group A - patients with creatinine clearance (CrCl) between 30 and 60 mL/min, Group B - patients with CrCl <30 mL/min not on dialysis, and Group C - patients with CrCl < 30mL/min who are on dialysis. Secondary endpoints included response rate, progression free survival and overall survival. Methods: Eligible patients had previously treated MM with renal impairment defined as creatinine clearance < 60 mL/min measured within 21 days prior to registration. Patients previously treated with lenalidomide were required to demonstrate clinical response (any duration) or stable disease with progression-free interval of > 6 months from start of that therapy. All patients received dexamethasone 40 mg orally on days 1, 8, 15 and 22 of a 28-day cycle. Prophylactic anticoagulation consisted of either 81 mg or 325 mg per day of aspirin. Patients also received lenalidomide orally every 1 or 2 days on days 1 through 21 of a 28-day cycle, as described below (Table 1). Starting doses were as in US Product Insert. Dose escalation follows a standard 3+3 design. Results: There have been 23 patients enrolled into groups and cohorts as shown in Table 1. Median age was 73 (range 49–89) and 13 (57%) were women. ISS stage was advanced in all patients, 0 in stage 1, 4 (18%) in stage 2 and 19 (82%) in stage 3. The regimen was well tolerated. Indeed, the MTD has not been reached in any of the groups, as no DLTs have occurred to date. The most commonly reported clinical adverse events (all grades, independent of attribution) across all patients included infections, hyperglycemia, constipation, dizziness, hyponatremia, hypocalcemia and tremor. Hematological toxicities (grade 3–4) occurred in 13 out of 21 pts (62%), mostly neutropenia and thrombocytopenia. Grade 3–4 events at least possibly related to the regimen occurred in 70% and included pneumonia (26%) and otitis media (9%). Response was seen in 14 patients, resulting in an overall response rate of 61%. CR was seen in 1 patient (4%), VGPR in 2 patients (9%), PR in 11 patients (43%), and SD for 9 patients. With median follow-up of 15.5 months, median progression-free survival is 9.8 months and median overall survival is 22 months. Conclusion: Lenalidomide and dexamethasone is a safe and effective regimen in patients with multiple myeloma and renal insufficiency. It is also very well tolerated, although cytopenias are common but manageable. MTD has yet to be reached in each group, allowing for higher doses to be given than previously thought, including 25mg daily (for 21/28 days) in patients with CrCl 30–60 mL/min, 25 mg every other day (for 21/28 days) in patients with CrCl < 30 mL/min not on dialysis, and 10mg daily (for 21/28 days) in patients with CrCl < 30 mL/min on dialysis. These results will provide needed, clinically relevant dosing for lenalidomide in MM patients with renal insufficiency. Disclosures: Kaufman: Millenium: Consultancy; Onyx: Consultancy; Celgene: Consultancy; Novartis: Consultancy.

The role of proinflammatory immune (IFN-gamma) gene signature in predicting prognosis and response to chemotherapy in uterine carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14209-e14209
Author(s):  
Haider Mahdi ◽  
Peter Graham Rose ◽  
Fadi W Abdul-Karim ◽  
Bradley J. Monk ◽  
Ying Ni
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Overall Survival ◽  
T Cells ◽  
Progression Free Survival ◽  
Gene Signature ◽  
Free Survival ◽  
High Stage ◽  
Response To Chemotherapy ◽  
Ifn Γ

e14209 Background: Immunotherapy is promising option given low toxicity and potential durable response. In mismatch repair proficient endometrial and ovarian cancers, the reported response rate is ranging from 10-15% in recurrent setting. We need to better identify subset of patients who benefits from immunotherapy. Multigene immune signatures represent a robust means of capturing a complex, T cell–inflamed phenotype necessary for the clinical activity of PD-1–/PD-L1–directed monoclonal antibodies. IFN-γ is a key cytokine produced by activated T cells, as well as natural killer (NK) and NK T cells, in the tumor microenvironment. An immune-related IFN-γ 18-gene profile was derived through a cross-validated penalized regression modeling strategy to predict response to anti-PD1 therapy across 9 different tumor types. We want to test if this gene panel can also predict cancer outcome and response to chemotherapy. Methods: We used whole transcriptome sequencing of RNA matched tumor-normal samples from 38 high stage (Stage III and IV) uterine serous cancer patients. All patients received chemotherapy with platinum and taxanes. IFN-18 gene expression score was calculated by averaging the normalized and log transformed individual gene read counts. The optimized score cut off was selected to best separating the progression free survival. Then the cut off score was tested in The Cancer Genomic Atlas (TCGA) uterine and ovarian cancer RNAseq datasets. Results: The IFN score of 2.46 was determined based on 18-gene expression derived from 38 high-stage uterine serous cancer samples. Average age was 67 years (range: 56-82 years). Uterine serous cancer is known to be MSI stable. Patients with score higher than 2.46 showed significantly longer progression free survival (PFS – 57.6 months vs 15months, p = 0.002) and longer overall survival (73.1 months vs 51.1 months), not statistically significant given our small sample size, p = 0.13) compared to the patients with score lower than 2.46. Then this IFN based gene signature was then applied to TCGA 541 uterine cancer samples with RNAseq data. Similarly, this signature predicted significant improvement in both progression-free survival (p = 0.001) and overall survival (p = 0.005). Interestingly, this score cannot separate outcome for TCGA ovarian cancer cohort. Conclusions: Immune-related IFN-γ gene signature predicted prognosis and response to chemotherapy. We plan to assess if this signature will predict endometrial cancer patients who benefits from anti-PD1 therapy.

Prognostic Implications of the Differentiation Inhibitory Factornm23-H1 Protein in the Plasma of Aggressive Non-Hodgkin’s Lymphoma

Blood ◽  
1999 ◽  
Vol 94 (10) ◽  
pp. 3541-3550 ◽  
Author(s):  
Nozomi Niitsu ◽  
Junko Okabe-Kado ◽  
Takashi Kasukabe ◽  
Yuri Yamamoto-Yamaguchi ◽  
Masanori Umeda ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Hodgkin’S Lymphoma ◽  
Progression Free Survival ◽  
Hodgkin's Lymphoma ◽  
Enzyme Linked Immunosorbent Assay ◽  
Free Survival ◽  
Non Hodgkin’S Lymphoma ◽  
Response To Chemotherapy ◽  
Non Hodgkin's Lymphoma

The outcome of patients with non-Hodgkin’s lymphoma has been improved by current approaches to treatment. Nevertheless, many patients either do not have a complete remission or ultimately relapse. To identify such patients, it is important to be able to predict the outcome. We previously found that the differentiation inhibitory factor/nm23 was correlated with the prognosis of acute myeloid leukemia. To examine the prognostic effect of nm23 on non-Hodgkin’s lymphoma, we established an enzyme-linked immunosorbent assay procedure to determine nm23-H1 protein levels in plasma and assessed the association of this protein level with the response to chemotherapy, overall survival, and progression-free survival in patients with aggressive non-Hodgkin’s lymphoma. The plasma concentration of nm23-H1 was significantly higher in patients with malignant lymphoma than in normal controls, especially in aggressive non-Hodgkin’s lymphoma. The complete remission rate in patients with higher nm23-H1 levels was significantly worse than that in patients with lower nm23-H1 levels. Overall survival and progression-free survival were also lower in patients with higher nm23-H1 levels than in those with lower levels. The 3-year survival rates in patients with low and high nm23-H1levels were 79.5% and 6.7% (P = .0001). A multivariate analysis of prognostic factors showed that the plasma nm23-H1level was independently associated with the survival and progression-free survival. An elevated plasma nm23-H1concentration predicts a poor outcome of advanced non-Hodgkin’s lymphoma. Therefore, nm23-H1 in plasma may be useful for identifying a distinct group of patients at very high risk.

Outcomes after Autologous Stem Cell Transplantation for Mantle Cell Lymphoma Based on Remission Status and Induction Chemotherapy Regimen.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1905-1905
Author(s):  
Brian G. Till ◽  
Theodore A. Gooley ◽  
Nathan Crawford ◽  
Ajay K. Gopal ◽  
David G. Maloney ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Refractory Disease ◽  
Free Survival ◽  
Remission Status ◽  
Kaplan Meier ◽  
Mantle Cell ◽  
Induction Regimen

Abstract Mantle cell lymphoma (MCL) has one of the worst prognoses of any subtype of non-Hodgkin’s lymphoma (NHL), with a median survival of 3–4 years in most series. High-dose therapy followed by autologous stem cell transplantation (ASCT) is an increasingly common treatment approach for MCL, and some ASCT studies suggest that less heavily pre-treated patients have a longer duration of progression-free survival (PFS), suggesting that ASCT may lead to more favorable outcomes if used earlier in the course of therapy. We analyzed the outcomes of ASCT with respect to remission status at the time of transplantation and induction regimen used in 56 consecutive transplanted patients with MCL. Twenty-one patients received induction chemotherapy with HyperCVAD with or without rituximab (±R) followed by ASCT in first complete or partial remission (CR1/PR1), 15 received CHOP (±R) followed by ASCT in CR1/PR1, and 20 received ASCT following disease progression. A variety of conditioning regimens were used for ASCT in all 3 groups. Estimates of overall (OS) and progression-free survival (PFS) at 3 years among patients transplanted in CR1/PR1 were 93% and 63%, compared with 46% and 36% for patients transplanted with relapsed or refractory disease, respectively (Figure 1). The hazard of mortality among patients transplanted with relapsed or refractory disease was 6.09 times that of patients transplanted in CR1/PR1 (P=.006). Patients in the CHOP (±R) group appeared to have a higher risk of failure for PFS compared to patients in the HyperCVAD (±R) group, though the difference did not reach statistical significance (hazard ratio [HR] 3.67, P=.11) with the small sample size available. The estimated 3-year PFS was 81% for patients in the HyperCVAD group and 44% for patients in the CHOP group. Patients who received R with induction therapy had a reduced risk of mortality (HR 0.33, P=.05) and failure for PFS (HR 0.28, P=.005) compared to those who did not. In summary, these results suggest that ASCT in first remission leads to improved survival outcomes for patients with MCL compared to ASCT with relapsed or refractory disease, and a HyperCVAD (±R) induction regimen may be associated with an improved PFS among patients transplanted in CR1/PR1. Figure 1. Kaplan-Meier estimates of overall survival from the time of ASCT, with respect to remission status at ASCT. Figure 1. Kaplan-Meier estimates of overall survival from the time of ASCT, with respect to remission status at ASCT.

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