Tolerance and Response to Initial Systemic Therapy In Older Patients with Follicular Lymphoma (FL): Observations From 186 Unselected Recent Cases In the Practices of US-Based Medical Oncologists (MOs).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3842-3842
Author(s):  
Neil Love ◽  
Stephanie A. Gregory ◽  
Bruce D. Cheson ◽  
Myron S. Czuczman ◽  
Melanie Elder ◽  
...  
Keyword(s):  
Side Effects ◽  
Board Of Directors ◽  
Older Patients ◽  
Age Groups ◽  
Treatment Selection ◽  
Phase Iii ◽  
Published Data ◽  
Advisory Committees ◽  
Presenting Symptoms ◽  
The Impact

Abstract Abstract 3842 Background: Advanced-stage FL is generally considered incurable, but the disease often responds to systemic anticancer treatment (SAT). A number of factors influence the selection of a specific SAT, which must be administered judiciously to older patients, particularly those with known comorbidities. A paucity of information exists to document which SATs are chosen for this population in clinical practice and the resultant clinical outcomes. We attempted to address this issue by aggregating and examining clinical information on individual patients receiving initial treatment for FL. Methods: US community-based MOs were recruited from a database of past participants in our CME activities to provide anonymous information on the presenting symptoms, diagnostic workup, treatment selection, side effects and clinical antitumor responses for all patients in their practices with a new diagnosis of FL since January 1, 2008. Modest, per-patient honoraria were provided to each MO for this work. Results: From April 14 to July 9, 2010, 38 MOs entered a total of 186 cases of FL into a web-based data bank (minimum 1 case, maximum 15, median 4.5). The median age was 66, with 45% under age 65, 26% from 65 to 74 and 29% age 75 and older. 53% of the patients were women. 42% of patients were minimally symptomatic or asymptomatic at diagnosis (Table 1), and across each of the three age groups the presence of various symptomology was similar. A number of SATs were initiated, including R-CHOP (26%), RCVP (25%), and rituximab monotherapy (13%). 15% of patients were observed without SAT. For patients first treated in 2010, an increase in the use of bendamustine/rituximab was observed, representing 8 of 26 patients (31%) versus 3 out of 80 patients (4%) in 2009. The choice of regimen differed by age, with, for example, more R-CHOP (37%) used for patients under age 65 and more R-CVP (38%) and rituximab monotherapy (28%) selected for patients age 75 and older. Overall, these treatments resulted in complete clinical responses in 57% of patients and “things went very well with expected or fewer toxicities” in 58%. These outcomes are similar to what has been reported in published data from randomized Phase III trials of these regimens. No major differences were observed in the levels of efficacy and side effects between the three age groups (Table 1). Conclusions: This unselected case series produced, in a rapid manner, information addressing a variety of clinical issues in newly diagnosed FL, including the impact of age on treatment selection and resultant outcomes. These data suggest that MOs are able to individualize SATs for older patients and match the short-term outcomes and tolerability of the therapies selected for younger patients. This risk-benefit differential is of particular palliative importance as this dataset demonstrates a majority of patients present with clinically significant tumor-related symptoms at diagnosis. Additional work of this kind is needed to better understand how physicians adjust the dose and schedule of SATs to prevent and ameliorate toxicity, particularly in older patients. Disclosures: Gregory: Cephalon Inc: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc: Consultancy; Genentech BioOncology: Consultancy, Speakers Bureau; Novartis Pharmaceuticals: Consultancy; Spectrum Pharmaceuticals: Consultancy. Cheson:Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Cephalon Inc: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Millenium Pharmaceuticals Inc: Membership on an entity's Board of Directors or advisory committees; Pfizer Inc: Membership on an entity's Board of Directors or advisory committees. Czuczman:Amgen Inc: Membership on an entity's Board of Directors or advisory committees; Biogen Idec: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Cephalon Inc: Membership on an entity's Board of Directors or advisory committees; Genentech BioOncology: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Lilly USA LLC: Membership on an entity's Board of Directors or advisory committees; Millenium Pharmaceuticals Inc: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees.

Tolerance and Response to Initial Systemic Therapy In Older Patients with Multiple Myeloma (MM): Observations From 276 Unselected Recent Cases In the Practices of US-Based Medical Oncologists (MOs)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1516-1516
Author(s):  
Neil Love ◽  
Sagar Lonial ◽  
Kenneth C. Anderson ◽  
Rafael Fonseca ◽  
Melanie Elder ◽  
...  
Keyword(s):  
Side Effects ◽  
Board Of Directors ◽  
Older Patients ◽  
Research Funding ◽  
Age Groups ◽  
Treatment Selection ◽  
Phase Iii ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Selection Of

Abstract Abstract 1516 Background: MM is generally considered incurable, but the rapid integration of IMiDs.. and proteasome inhibitors into systemic anticancer treatment (SAT) has resulted in clinically important improvements in response rates, disease control and overall survival. A number of factors — including age and comorbidities — influence selection of an initial SAT and whether autologous stem cell transplant (ASCT) is planned. A paucity of information exists on selection of specific SATs for patients in different age groups and resultant outcomes. We attempted to address this issue by aggregating and examining clinical information on individual patients receiving initial treatment for MM. Methods: US community-based MOs were recruited from a database of past participants in our CME activities to provide anonymous information on the presenting symptoms, diagnostic workup, treatment selection, side effects and clinical antitumor response for all patients in their practices with a new diagnosis of MM since January 1, 2008. Modest, per-patient honoraria were provided to each MO for this work. Results: From April 14 to July 9, 2010, 43 MOs entered a total of 276 cases of MM into a web-based data bank (minimum 1 case, maximum 14, median 6). 54% of the patients were men. The median age was 68, with 34% under age 65, 36% from 65 to 74 and 30% age 75 or older. 88% of patients had their tumors evaluated by FISH and/or metaphase cytogenetics. 73% of the evaluated specimens were considered to be “standard risk” and 27% were determined to be “poor risk.” 67% of patients were considered very or moderately symptomatic from the disease at the time treatment was initiated (Table 1), and similar fractions of patients presented with various levels of symptomology across the three age groups. 128 patients (46%) were deemed eligible for ASCT (maximum age 78), and 59 of these patients had already received ASCT after induction treatment. The median age of patients eligible for ASCT was 62, and the most common induction SATs for these patients were Rd or RD (29%), RVD (26%) and VD (23%). The median age of patients considered ineligible for transplant was 76.5, and the most common induction SATs were VD (22%) Rd or RD (21%) MPT (17%) and MPV (17%). Overall, these treatments resulted in CR and PR rates of 22% and 64% respectively, and “things went very well with expected or fewer toxicities” in 38% and minor or moderate toxicity in 44%. These outcomes are similar to what has been reported in published trial data from randomized Phase III studies of these regimens. No major differences were observed in reported levels of efficacy and side effects among the three age groups (Table 1). Conclusions: This unselected case series produced, in a rapid manner, useful information addressing a variety of clinical issues in newly diagnosed MM, including the impact of age and transplant status on treatment selection and outcomes. These data suggest that MOs are able to individualize SATs for older patients and match the short-term outcomes of the therapies they select for younger patients. This risk-benefit differential is of particular palliative importance as these data demonstrate that at diagnosis most patients present with tumor-related symptoms. Additional work of this kind is needed to better understand how physicians adjust doses and schedules of SATs to prevent and ameliorate toxicity, particularly in older patients. Disclosures: Lonial: Bristo-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium Pharmaceuticals Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Anderson:Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millenium Pharmaceuticals Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onxy Pharmaceuticals Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees. Fonseca:Amgen Inc: Consultancy; Bristol-Myers Squibb: Consultancy; Celgene Corporation: Consultancy, Research Funding; Genzyme Corporation: Consultancy; Medtronic Inc: Consultancy; Otsuka Pharmaceutical Co Ltd: Consultancy; Onyx Pharmaceuticals: Research Funding.

scholarly journals Patient Characteristics and Outcomes in Adolescents and Young Adults (AYA) with Acute Myeloid Leukemia (AML): Princess Margaret Cancer Centre Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2609-2609
Author(s):  
Muhned Alhumaid ◽  
Georgina S Daher-Reyes ◽  
Wilson Lam ◽  
Arjun Law ◽  
Tracy Murphy ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Age Groups ◽  
Treatment Strategies ◽  
Patient Characteristics ◽  
Cancer Center ◽  
Advisory Committees ◽  
Disease Behavior

Introduction: Clinical outcomes of acute myeloid leukemia (AML) in adolescents and young adults (AYA) are rarely reported as an isolated subgroup. Treatments vary little across age groups, and treatment intensity depends upon comorbid conditions and performance status. Optimal treatment strategies focused on disease behavior, biological factors, and the distinct needs of this subset of AML patients remain elusive. The purpose of this retrospective analysis is to determine the characteristics and outcomes of AYA AML patients treated at a specialized adult leukemia cancer center in comparison to older adults with AML (40-60 years). Methods: A retrospective analysis was performed on all patients treated at Princess Margaret Cancer Center from 2008-2018. Patients with acute promyelocytic leukemia were excluded. Clinical characteristics, treatment strategies, and survival outcomes were recorded for all patients. Overall survival (OS) and disease-free survival (DFS) rates were calculated using the Kaplan-Meier product-limit method and the impact of covariates were assessed using the Log-rank test. Finally, we compared the outcomes of AYA patients treated at our centre between 2015-2018 with older patients. Results: A total of 175 patients aged 18-39 were identified. Patient characteristics are shown in (Table 1). Cytogenetic were available in 163 patients. Based on MRC criteria, 27 (16%) were favorable risk, intermediate in 95 (54%), adverse in 39 (22%), and missing/failed in 14(8%). NPM1 status was available in 110 patients of whom 38 (35%) were positive. FLT3-ITD was available in 67 patients with 24 (36%) positive. Both mutations were present in 13 (54%) patients. There were no significant differences in terms of risk stratification based on cytogenetic and molecular markers based on age (18-29 vs.30-39) (P= 0.98). Most patients 172 (98%) received induction, 157 (91%) with 3+7, and 15 (9%) with FLAG-IDA. Complete remission (CR) was achieved in 133 (77%) after first induction [120 (76%) after 3+7 and 11 (73%) after FLAG-IDA]. Induction related mortality was low (2%). Of the 39 who did not achieve CR, thirty-four patients received re-induction (13 FLAG-IDA, 16 NOVE-HiDAC, 5 others) with CR in 21 (62%). Overall, 154 (89.5%) achieved CR1. Sixty-four (42%) proceeded to hematopoietic stem cell transplantation (HSCT) in CR1. 59 (38%) patients relapsed in CR1 with 8 (12%) relapsing post HSCT. Fifty-five (5 post HSCT) patients received reinduction with 30 (51%) (2 after HSCT) achieving CR2. Fifteen patients received HSCT in CR2. OS and DFS at 2 years were 62% (95% CI 0.53-0.69) and 50% (95% CI 0.41-0.57), respectively. Stratified by cytogenetic risk, OS was 81% for favorable risk, 61% for intermediate, and 50% for adverse risk (P=0.0001), respectively. DFS in these groups was 85%, 57%, and 46 % (P=0.0025), respectively. We further compared outcomes in the 18-29y and 30-39y age groups. The OS was 61.9% compared to 62.5% (P=0.91) and DFS of 52.1% compared to 47% (P=0.65) respectively. On univariate analysis for OS and DFS, cytogenetic risk stratification was the only significant variable (P=0.0004 and P=0.0042). We then compared the outcomes 67 sequential patients aged I8-39 treated from 2014-2018, with those of 176 sequential patients aged 40-60 treated during the same period (table 2). OS at 2 years was not statistically higher in the younger group compared to the older group (66.7% vs. 61.2%, P=0.372). While relapse rate was lower in older patients (15.5% vs. 22.6%, P=0.093), NRM was higher in older patients (29.7% vs. 18.8%,P=0.094). Conclusion: AYA pts. occupy a unique niche amongst AML as a whole. While treatment responses have improved in general, there may be potential for further gains in these patients. Increased tolerance for more intense treatment strategies as well as the incorporation of novel agents into standard treatment protocols may provide a means to optimize care in AYA patients. Finally, research is needed to elucidate biological mechanisms and predictors of disease behavior instead of arbitrary, age-stratified treatment schema. Disclosures McNamara: Novartis Pharmaceutical Canada Inc.: Consultancy. Schimmer:Jazz Pharmaceuticals: Consultancy; Medivir Pharmaceuticals: Research Funding; Novartis Pharmaceuticals: Consultancy; Otsuka Pharmaceuticals: Consultancy. Schuh:Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Teva Canada Innovation: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Honoraria; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees. Maze:Pfizer Inc: Consultancy; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Yee:Astellas: Membership on an entity's Board of Directors or advisory committees; Millennium: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Astex: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MedImmune: Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Hoffman La Roche: Research Funding. Minden:Trillium Therapetuics: Other: licensing agreement. Gupta:Incyte: Honoraria, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sierra Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees.

PCR-Based Minimal Residual Disease (MRD) Detection Is a Strong Independent Outcome Predictor Also in Rituximab-Intensive Non-ASCT-Based Programs: Results From the ML17638 Multicenter Randomised Phase III Trial for Elderly Follicular Lymphoma (FL) Patients of the Fondazione Italiana Linfomi (FIL)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 787-787
Author(s):  
Marco Ladetto ◽  
Chiara Lobetti-Bodoni ◽  
Barbara Mantoan ◽  
Andrea Evangelista ◽  
Carola Boccomini ◽  
...  
Keyword(s):  
Molecular Marker ◽  
Board Of Directors ◽  
Residual Disease ◽  
Monitoring Program ◽  
Clinical Results ◽  
Phase Iii ◽  
Outcome Predictor ◽  
Advisory Committees ◽  
The Impact

Abstract Abstract 787 Background: Many studies support the value of PCR-based MRD detection using the bcl-2-IgH translocation as an outcome predictor in FL but some failed to confirm this observation. Concerns have been raised particularly for programs which are highly Rituximab (Rtx) intensive (with or without maintenance) and non-ASCT-based. The ML17638 study, contained an extensive centralized MRD monitoring program, whose results are here presented. Patients and methods: Clinical results of study have been already reported (Vitolo et al, ASH 2011). The program consisted of 4 R-FND courses (Rtx, fludarabine, mitoxantrone, dexamethasone) followed by 4 doses of weekly Rtx. Patients (pts) achieving 3partial response (PR) were randomized to Rtx maintenance (arm A) or observation (arm B). A total of 234 untreated elderly (age 60–75 years) pts at diagnosis were enrolled. With a median follow-up from randomization of 34 months, 3-year PFS and OS were 66% (95%CI:59-72%) and 89% (95%CI:85-93%), with a clear trend in favor of arm A for 2-year PFS (81% vs 69%). At enrolment, pts were screened for a molecular marker based on the bcl-2/IgH MBR or mcr. If found, pts were tested at 8 fixed timepoints: at month 5 (M5) after 4-R-FND, at the end of induction therapy (M8) and during maintenance/observation and follow-up (M12,M18,M24,M30,M36 and M42) or until relapse. MRD was assessed by both nested PCR (n-PCR) and real time quantitative PCR (RQ-PCR) on BM cells. Methods have been already reported (Ladetto Exp Hematol 2001). RQ-PCR was performed and analyzed according to the Euro-MRD guidelines (Van der Velden Leukemia 2007). The lab performs routine quality controls in the context of Euro-MRD and was blinded to clinical results and radomization arm. The impact of MRD on PFS was evaluated by log-rank tests and Cox models including age, sex, FLIPI, ECOG PS and complete remission (CR). In addition, the effect of PCR negativity on PFS during the whole follow-up period was evaluated by a time-varying covariate included in the models, also considered in a cumulative way (0, 1, 2, 3 or more consecutive PCR-negative timepoints). Results: 229 of 234 enrolled pts (98%) were screened at study entry. A molecular marker was found in 118 (51.5%). Of these, 9 were excluded due to withdrawal before M5 (7) or inadequate sampling (2). Overall, 800 follow-up samples were expected. Of these, 707 (88%) were received and analysed: 98% of pts were evaluable for 350% of timepoints and 87% for 375%. Pts with and without a marker had identical PFS (61% at 42m for both). Sixty six per cent of pts achieved PCR-negativity after R-FND and 81% at the end of treatment, with a mean tumor burden reduction of 11 natural logaritm after R-FND and a further decrease of 1.6 after the 4 weekly Rtx. At randomization, PCR-positivity rate was similar in the two arms while during and after maintenance pts in Arm A had a lower rate of PCR-positivity (9% vs 17% p=0.02). The achievement of PCR-negativity by both n-PCR and RQ-PCR at timepoints M8,12,18 and 24 predicted a better PFS (M5 not predictive, M30, 36, 42 have too early follow up for meaningful evaluation). After M8, 2-year PFS was significantly better in PCR-negative than PCR-positive pts: 72% vs 39% (p=0.007, Fig. 1). Achieving a double PCR-negativity at M8-M12 or triple molecular negativity at M8-M12-M18 was associated with a further increase of PFS (82% vs 46% for months 8–12, p=0.001 and 87% vs 53% for months 8–12-18, p=0.001). PCR-negativity at M8 ensured a subsequent better PFS both in CR (p=0.023, HR=0.33, 95%CI: 0.13–0.86) and PR (p=0.074, HR=0.28, 95%CI: 0.07–1.13) pts (Fig. 2). Disclosures: Ladetto: Hoffman-La Roche: Consultancy, Honoraria. Rossi:Roche: Honoraria. Musto:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Gamba:Roche: Employment. Vitolo:Celgene: Honoraria; Janssin-Cilag: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Impact of Age, Comorbidity, and Polypharmacy on Treatment and Survival for Aggressive Non-Hodgkin Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 26-27
Author(s):  
Laura Tapley ◽  
Pamela Skrabek ◽  
Pascal Lambert ◽  
Jenniebie Bravo ◽  
Kathleen Decker ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Proportional Hazards ◽  
Hematologic Malignancy ◽  
Age Groups ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Advisory Committees ◽  
Substantial Impact ◽  
Curative Therapy ◽  
The Impact

Introduction: Non-Hodgkin's lymphoma (NHL) is the most prevalent hematologic malignancy, with most people diagnosed aged over 65 years (Alexander et. al. Int.J.Cancer 2007). Older populations have more comorbid health conditions, frailty, polypharmacy, and health resource use (Ogle et. al. Cancer 2000). The complex interplay of these factors may influence the prescription of curative therapy and prognosis. In trials evaluating NHL therapies, elderly patients are underrepresented, particularly those with frailty or comorbidity, resulting in knowledge gaps. We report a retrospective, population-based cohort study of aggressive NHL patients and examine the impact of age and its interaction with comorbidity and polypharmacy on treatment patterns and survival. Methods: Using the Manitoba Cancer Registry we identified patients aged over 18 years with NHL diagnosed from 2004-2015. We limited the cohort to aggressive NHL types using morphology codes. Data on demographics, stage, NHL type, comorbidities, polypharmacy, and chemotherapy were obtained from population-based provincial databases. Comorbidity was measured using Johns Hopkins ACG System software, which factored in all measured hospital-based and outpatient medical services utilized and collapsed them into one of six Resource Utilization Band (RUB) categories, from no use to very high user. Overall survival (OS) was calculated using Kaplan-Meier curves. Cox proportional hazards regression models were constructed to determine the interaction of age with a variety of factors. Multi-variable logistic regression was also used to examine the receipt of chemotherapy and the interaction with age. Results: In our cohort of 1,073 patients with aggressive NHL, 704 were treated with systemic chemotherapy. Treatment rates decreased with increasing age and medication count, while stage and comorbidity had little impact (Table 1). Median OS decreased with age among treated patients and was very short without chemotherapy (Table 1). Multivariate analyses found that individuals with increasing age, stage III, unknown stage, histology other than DLBCL, and higher medication counts were less likely to receive chemotherapy. For the receipt of chemotherapy, no age interactions were found. In addition, in patients who received chemotherapy, increased age and stage were associated with poorer survival, while more recent year of diagnosis improved survival. No age interactions with a substantial impact on survival were found. Conclusions: OS in aggressive NHL diminishes with increasing age, but is longer in those receiving chemotherapy across all age groups. Comorbidity and medication count influenced the receipt of chemotherapy and OS. Higher medication count was only independently associated with less likelihood of receiving chemotherapy, while comorbidity was not independent of other factors for either receipt of chemotherapy or OS. Disclosures Dawe: AstraZeneca Canada: Research Funding; AstraZeneca Canada: Membership on an entity's Board of Directors or advisory committees; Boehringer-Ingelheim: Honoraria; Merck Canada: Membership on an entity's Board of Directors or advisory committees.

Comparison of Outcomes of Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide in Older Versus Younger Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-27
Author(s):  
Giacomo Adoncecchi ◽  
Ambuj Kumar ◽  
Rawan Faramand ◽  
Hien D. Liu ◽  
Farhad Khimani ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Older Patients ◽  
Research Funding ◽  
Chronic Gvhd ◽  
Age Groups ◽  
Group Versus ◽  
Survival Outcomes ◽  
Advisory Committees ◽  
Younger Patients ◽  
Two Age Groups

Introduction: Previous studies have demonstrated that allogeneic haploidentical (haplo) peripheral blood stem cell transplantation (PBSCT) with post-transplant cyclophosphamide (PTCy) yields improved progression free survival (PFS) when compared to haplo bone marrow transplant (BMT) with PTCy, attributable to lower relapse without an increase in non-relapse mortality (NRM) (Bashey, et al. JCO. 2017). However, haplo PBSCT results in higher rates of graft-versus-host disease (GVHD) which may negate these benefits in older patients who are more susceptible to transplant related toxicity. Thus, evaluation of the outcomes of haplo PBSCT with PTCy in older patients is warranted. Methods: We retrospectively evaluated 121 adult patients with hematologic malignancies treated at the Moffitt Cancer Center with allogeneic T-cell replete PBSCT from a haplo donor followed by PTCy-based GVHD prophylaxis. Data were extracted from the Moffitt BMT Research & Analysis Information Network (BRAIN) database. Myeloablative (n=70, 58%) and reduced intensity (n=51, 42%) conditioning regimens were included. Transplant related outcomes were compared between two age groups: <60 years (n=66) versus >60 years (n=55). Associations with transplant related survival outcomes were assessed using univariate and multivariate Cox proportional hazard survival models. Fine and Gray regression models were used to assess associations of transplant related endpoints with competing risks. Kaplan-Meier curves and cumulative incidence function curves were also plotted. Results: The median age at the time of transplant was 42 years (range: 20-59) for the younger group and 66 years (range: 61-75) for the older group. The median follow-up was 17 months (range: 2-53) for the entire cohort. Younger patients were more likely to receive myeloablative conditioning (83% versus 27%, p<0.001). Baseline characteristics were otherwise similar. Neutrophil engraftment (>500/uL) by day 30 did not differ significantly between the younger and older group (98% versus 93%, p=0.26). However, the median time to neutrophil engraftment was faster in the younger group versus the older group (16 versus 21 days, p<0.001). Platelet engraftment (>20,000/uL) by day 90 was achieved in 92% in the younger group versus 76% in the older group (p=0.03). The time to platelet engraftment was faster in the younger group: 28 days versus 36 days (p=0.006). At day 100, the cumulative incidence (CuI) of grade II-IV acute GVHD in younger patients was 42% (95% CI 29-61%) and for older patients was 35% (95% CI 22-55%, p=0.82). The CuI for grade III-IV acute GVHD for the younger and the older groups were 8% (95% CI 4-25%) and 15% (95% CI 7-38%, p=0.23), respectively. At 2 years, the CuI of chronic GVHD was 67% (95% CI 55-82%) for younger patients versus 56% (95% CI 38-82%) for older patients (p=0.20). NRM for the younger group and the older group, respectively, was 6% (95% CI 2-16%) versus 19% (95% CI 11-34%) at 100 days and 14% (95% CI 6-30%) versus 22% (95% CI 13-37%) at 2 years (p=0.17). The CuI of relapse at 2 years was not significantly different between the two age groups, with the younger recipients having a CuI of 42% (95% CI 20-60%) and the older group 31% (95% CI 17-56%, p=0.70). The 2-year DFS was similar between the younger and older group, respectively: 51% (95% CI 36-66%) and 53% (95% CI 37-70%, p=0.72). Similarly 2-year overall survival (OS) for the younger group was 59% (95% CI 44-74%), while the older group was 66% (95% CI 52-80%, p=0.92). In multivariate analysis, NRM was superior in the younger group (HR=0.31, 95% 0.12-0.82, p=0.02). Otherwise, age was not associated with engraftment, risk of acute or chronic GVHD, relapse, DFS, or OS. Conclusion: Our results demonstrate that outcomes following allogeneic haplo PBSCT with PTCy in patients >60 years approximate outcomes in patients <60 years. While NRM was inferior in the older patient group, this difference did not result in significant differences in long term OS or DFS. Instead, other variables such as the hematopoietic comorbidity index and the disease risk index were better indicators of survival outcomes. Additionally, these survival outcomes with haplo PBSCT with PTCy appear to be similar to prior published data with haplo BMT with PTCy in older patients (Kasamon, et al. JCO. 2015). Based on this study, haplo PBSCT with PTCy is an appropriate transplant platform for elderly patients. Disclosures Khimani: Bristol Myers Squibb-Moffitt-Alliance: Research Funding. Nishihori:Novartis: Other: Research support to institution; Karyopharm: Other: Research support to institution. Pidala:Syndax: Consultancy, Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Takeda: Research Funding; Janssen: Research Funding; Johnson and Johnson: Research Funding; Pharmacyclics: Research Funding; Abbvie: Research Funding; BMS: Research Funding. Bejanyan:Kiadis Pharma: Membership on an entity's Board of Directors or advisory committees.

Incidence of Vascular Thrombotic Events in 183 Consecutive Patients Treated with Nilotinib: A Single Centre Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3147-3147 ◽  
Author(s):  
James Gilbert ◽  
Simona Deplano ◽  
Richard Szydlo ◽  
Renuka Palanicawandar ◽  
Gareth Gerrard ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Side Effects ◽  
Adverse Events ◽  
Cardiovascular Risk Factors ◽  
Board Of Directors ◽  
Older Patients ◽  
Research Funding ◽  
Kinase Inhibitors ◽  
Advisory Committees

Abstract Introduction The spectrum of adverse events occurring in nilotinib is broadly similar to that of other tyrosine kinase inhibitors but recent reports suggest an increase in the incidence of vascular thrombotic events (VTE) compared to imatinib. Many patients treated with ponatinib, where the association of VTE with treatment is now widely accepted, have previously received nilotinib and it remains unclear as to whether the adverse events are a result of the cumulative use of the two drugs. It is important to clearly delineate the risk of VTE with nilotinib in order to estimate risk and provide better information for patients. Methods We conducted a chart review to identify adverse events in 183 consecutive patients who received nilotinib in our institution from February 2006 until June 2014. Patients were to be considered at risk of side effects in they had received at least 24 hours of treatment. Data were collected from out-patient consultations in which side effects and their severity were self-reported and recorded in the medical case notes. The cohort contained 93 women and 90 men and had a median age of 56 years (range 21-93). 8% of patients received nilotinib as first line therapy: 46% and 39% respectively were treated after failure of imatinib only or imatinib and dasatinib . The remainder were treated for relapse post allogeneic transplant. Of those who were treated after one or two prior tyrosine kinase inhibitors (TKI), 57% and 43% were intolerant or resistant respectively. Results The median duration of treatment with nilotinib was 714 days (range 10 -2816 days). Information was available for pre-existing cardiovascular risk factors in 93% of patients and were present in 59%. We recorded 20 occurrences of VTE in 10% of patients with 9 (5%), 7 (4%) and 4 (2%) episodes of myocardial ischaemia, peripheral arterial occlusive disease and cerebrovascular disease respectively. Only one patient without pre-existing cardiovascular risk factors experienced a VTE, The median age of patients with VTE was 67 years (range 35-79) compared to 55 years (range 21-93) in those without VTE. In contrast to previously reported results VTE were more common (18%) in patients who had received two prior TKI compared to 8% in those who had been treated with a single TKI and 7% who received nilotinib upfront. 75% of VTE occurred in patients who have been treated with nilotinib for more than 2 years but this may in part be because of continuation of treatment at a time of lack of awareness of the association of nilotinib with VTE. The remaining adverse events reported on nilotinib were in accordance with published data. Side effects occurring in >10% of patients are given in the table. Conclusions The incidence of VTE in patients treated with nilotinib in our institution was 10%. VTE was more frequent in older patients, in those with pre-existing cardiovascular risk factors and in those who received prolonged therapy with nilotinib. Without a suitable control group matched for age and cardiovascular risk factors it is difficult to provide an accurate estimate of any potential increased risk of treatment with nilotinib. Nevertheless caution must be exercised in older patients with pre-existing risks for VTE and appropriate counselling and monitoring provided. Table 1Adverse eventIncidence (%)Rash and/or pruritus43Fatigue31Elevated transaminases21Myalgia18Abdominal pain17Headaches17Arthralgia16Nausea14Thrombocytopenia12Neutropenia12Anaemia7 Disclosures Gerrard: Novartis: Research Funding. Foroni:Novartis: Research Funding. Apperley:Ariad Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Significant Survival Improvement with Maintenance in Patients Achieving a Complete Response: Pooled Analysis of 4 Italian Phase III Trials in Newly Diagnosed Multiple Myeloma Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1974-1974
Author(s):  
Chiara Cerrato ◽  
Francesca Gay ◽  
Maria Teresa Petrucci ◽  
Pellegrino Musto ◽  
Gianluca Gaidano ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Board Of Directors ◽  
Complete Response ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Advisory Boards ◽  
Phase Iii Trials ◽  
The Impact

Abstract Introduction Several trials have shown that maintenance therapy prolongs progression-free survival (PFS) in multiple myeloma (MM) patients, eligible and ineligible for autologous stem cell transplantation (ASCT); conflicting data exist about its impact on overall survival (OS). The role of maintenance in patients with a sensitive disease is still unclear. We conducted a retrospective pooled analysis to clarify the impact of continuous treatment in patients achieving a complete response (CR). Methods Data from newly diagnosed MM patientsenrolled in 4 phase III trials were analysed. Two trials included ASCT-eligible patients: RV-MM-209 [melphalan-prednisone-lenalidomide (MPR) vs melphalan 200 mg/m2 (Mel200), followed by lenalidomide maintenance vs no maintenance), RV-MM-EMN-441 (cyclophosphamide-lenalidomide-dexamethasone vs Mel200, followed by lenalidomide vs lenalidomide-prednisone maintenance). Two studies enrolled elderly, ASCT-ineligible patients: GIMEMA-MM0305 (bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide vs bortezomib-melphalan-prednisone) and EMN01 (MPR vs cyclophosphamide-prednisone-lenalidomide vs lenalidomide-dexamethasone, followed by lenalidomide vs lenalidomide-prednisone maintenance). The primary endpoint of the study was to evaluate the impact of maintenance on PFS and OS in patients who achieved CR. Univariate analyses of OS and PFS were performed. Response was considered as a time-dependent variable with a landmark point at 12 months. Lastly, a multivariate analysis was performed to evaluate the impact of maintenance and ASCT as independent variables. Results A total of 1964 patients were retrospectively analysed. Of 1503 patients who received maintenance therapy, 254 achieved a CR and 931 a very good partial response (VGPR) or partial response (PR). After a median follow-up of 41 months, a significant 5-year OS (80% vs 54%; HR 0.55, p=0.02; Figure 1) and 5-year PFS (52% vs 19%; HR 0.47, p<0.001; Figure 2) advantage was reported among CR patients who received maintenance in comparison with no maintenance. The same analysis was conducted in patients achieving a suboptimal response (VGPR or PR): the 5-year PFS advantage was confirmed in patients who received maintenance vs patients who did not (30% vs 13% HR 0.65, p<0.001); the 5-year OS was 68% vs 38% in patients who received maintenance vs no maintenance respectively (HR 0.8, p=0.2). A subgroup analysis was conducted in CR patients according to the treatment received [ASCT vs conventional chemotherapy (CC)]; the PFS benefit among patients treated with maintenance was confirmed across both the subgroups (ASCT group: HR 0.45, p=0.02; CC group: HR 0.45 P<0.001). In multivariate analysis, maintenance therapy and treatment with ASCT confirmed the favourable impact on PFS and OS in patients achieving CR. Conclusion In CR patients,maintenance therapy significantly prolongs PFS and OS. In order to optimize treatment efficacy and to prolong survival in patients with a sensitive disease, the intensification with maintenance is strongly recommended. Disclosures Off Label Use: Use off-label of drugs for the dose and/or schedule and/or association. Gay:Sanofi: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Gaidano:Novartis: Honoraria, Other: Advisory boards; Celgene: Research Funding; Karyopharm: Honoraria, Other: Advisory boards; Roche: Honoraria, Other: Advisory boards; Morphosys: Honoraria, Other: Advisory boards; GlaxoSmithKline: Honoraria, Other: Advisory boards; Amgen: Honoraria, Other: Advisory boards; Janssen: Honoraria, Other: Advisory boards. Offidani:Janssen-Cilag, Celgene, Sanofi, Amgen, Mundipharma: Honoraria. Patriarca:Janssen-Cilag, Celgene, Merck Sharp & Dohme: Honoraria. Di Raimondo:Janssen-Cilag, Celgene: Honoraria. Hájek:Janssen-Cilag: Honoraria; Celgene, Merck Sharp & Dohme: Consultancy, Honoraria. Boccadoro:Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees. Palumbo:Novartis, Sanofi Aventis: Honoraria; Celgene, Millennium Pharmaceuticals, Amgen, Bristol-Myers Squibb, Genmab, Janssen-Cilag, Onyx Pharmaceuticals: Consultancy, Honoraria.

scholarly journals Curriculum in Chronic Lymphocytic Leukemia Narrows the Educational Gaps of the Oncology Healthcare Team

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5878-5878
Author(s):  
Lauren Willis ◽  
Lisa Brauer ◽  
Emily S Van Laar ◽  
Patrick Kugel ◽  
Katie S Lucero ◽  
...  
Keyword(s):  
Side Effects ◽  
Chronic Lymphocytic Leukemia ◽  
Adverse Events ◽  
Board Of Directors ◽  
Research Funding ◽  
Treatment Selection ◽  
Lymphocytic Leukemia ◽  
Advisory Committees ◽  
Treatment Naïve ◽  
Educational Gaps

Introduction: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western world. Treatment selection in CLL is dependent upon a number of factors, such as patient age and genetic mutations, and can be challenging. A number of novel therapies and combination treatment approaches are now available, making treatment selection and management of adverse events increasingly complex. We sought to determine if a curriculum of online continuing professional education (CPE) activities could improve hematologists/oncologists (hem/onc, H/O), pathologists (path), nurse/NP, and pharmacist knowledge, competence, and confidence related to clinical decision making in patients with CLL. Methods: An expert panel identified educational gaps related to the treatment of patients with CLL. Based on the educational needs identified, the curriculum included 4 activities that were posted online between March 2019-June 2019. The first activity was a 30 minute video lecture (1 faculty) about measurable residual disease (MRD) analysis in CLL. The second activity was 30 minute video roundtable discussion (3 faculty) about treatment initiation and selection in newly diagnosed CLL. The third activity was a text activity focused on relapsed/refractory (R/R) CLL with 2 patient cases. The final activity was a video discussion between a nurse and pharmacist about mitigating side effects and optimizing compliance with oral therapies in CLL. Three activities were certified for physicians and the fourth activity was certified for nurses and pharmacists. Multiple-choice questions were asked before and after participation in each activity A repeated-pairs analysis was conducted where individual learners served as their own controls. Improved indicates an incorrect response pre-activity and a correct response post-activity. Reinforced indicates a correct answer pre- and post-activity. Improved confidence indicates a higher level of confidence post-activity. Results: As of July 2019, there were 356 hem/oncs, 154 pathologists, 178 nurses/NPs, and 504 pharmacists included in this analysis. The curriculum had a large impact on the knowledge and competence of hem/oncs and pathologists. MRD is an indicator of improved progression free survival: 13% H/O and path improved their knowledge, 58% H/O and 36% path reinforced their knowledge. The role for MRD measurement in CLL: 24% H/O and 15% of path improved their knowledge, 51% H/O and 39% path reinforced their knowledge. Selecting therapy for treatment-naïve CLL: 13% H/O and 30% path improved their competence, 57% H/O and 36% path reinforced their competence. Selecting therapy for relapsed/refractory (R/R) CLL: 39% H/O and 42% path improved their competence, 26% H/O and 11% path reinforced their competence. Managing treatment-related side effects in CLL: 11% H/O and 33% path improved their competence, 72% H/O and 31% path reinforced their competence. 10% of nurses/NPs and 11% of pharmacists improved and 30% of nurses/NPs and 38% of pharmacists reinforced their skills counseling patients about adverse event management and drug-drug interactions in R/R CLL. Tailoring frontline therapy in treatment-naïve CLL: 26% H/O and 15% path improved their confidence. Tailoring therapy in R/R CLL: 34% H/O and 31% path improved their confidence. Using MRD in CLL management: 31% H/O and 21% path improved their confidence. Improving patient engagement by using effective interprofessional communication: 25% nurses/NPs and 36% pharmacists improved their confidence. Conclusions: This analysis shows that an online CPE curriculum, utilizing many different formats (video, text, panel discussions) can improve and reinforce the knowledge, competence, and confidence of hem/oncs, pathologists, nurses/NPs, and pharmacists in multiple areas surrounding the treatment of patients with CLL. Results also suggest the following areas warrant further education: knowledge of the role for MRD in CLL management, individualizing therapy selection for treatment-naïve and R/R CLL, and managing treatment-related adverse events of CLL therapies. Acknowledgements: Sameer Bhagavatula contributed to data analysis for this research. Figure Disclosures Allan: Verastem Oncology, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy; Janssen: Consultancy, Honoraria; AbbVie, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acerta Pharma: Consultancy; Sunesis Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics LLC, an AbbVie company: Consultancy; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Awan:Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Janssen: Consultancy; Genentech: Consultancy; Sunesis: Consultancy; Gilead: Consultancy. Brander:AbbVie: Consultancy, Honoraria, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy; Tolero: Research Funding; DTRM Biopharma: Research Funding; BeiGene: Research Funding; MEI: Research Funding; Acerta: Research Funding; Novartis: Consultancy; Genentech: Consultancy, Honoraria, Research Funding; Teva: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Research Funding. Cohen:Genentech, Inc.: Consultancy, Research Funding; Janssen Pharmaceuticals: Consultancy; LAM Therapeutics: Research Funding; UNUM: Research Funding; Hutchison: Research Funding; Astra Zeneca: Research Funding; Lymphoma Research Foundation: Research Funding; ASH: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding. Barrientos:Pharmacyclics: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; Janssen: Consultancy; Gilead: Consultancy; Genentech: Consultancy.

Autologous Peripheral Blood Stem-Cell (PBSC) Collection Is Not Impaired by Bortezomib-Thalidomide-Dexamethasone (VTD) Induction Therapy in Newly Diagnosed Multiple Myeloma (MM)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 317-317 ◽  
Author(s):  
Annamaria Brioli ◽  
Giulia Perrone ◽  
Silvestro Volpe ◽  
Silvana Pasini ◽  
Anna Mele ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Phase Iii ◽  
Study Endpoint ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Cd34 Cells ◽  
Group 2 ◽  
The Impact

Abstract Abstract 317 Introduction: The novel agents bortezomib, thalidomide and lenalidomide have been successfully incorporated into autologous stem-cell transplantation (ASCT) as up-front therapy for newly diagnosed MM. However, several reports have raised concerns about the impact of novel agent-based induction regimens on PBSC collection. Furthermore, the ability to successfully collect PBSCs following initial therapy with two of these newer drugs needs to be confirmed in large phase III clinical trials. Methods: The GIMEMA Italian Myeloma Network designed a phase III study to compare VTD with thalidomide-dexamethasone (TD) as induction therapy prior to double ASCT. Primary study endpoint was the rate of complete or near complete response to each of these two induction regimens, while their toxicity profile – including the impact on PBSC mobilization and collection - was a secondary study endpoint. To address this latter issue, we performed a post-hoc analysis to compare the effect of the triplet VTD induction regimen versus the doublet TD combination on CD34+ cell collection. After three 21-day cycles of VTD or TD induction therapy, patients received intermediate dose cyclophosphamide (CTX 4 g/m2) followed by G-CSF (10 mcg/Kg/die) to mobilize and collect PBSCs. The target threshold to safely perform double ASCT was 4 × 106 CD34+ cells/Kg. Results: Patients evaluable for PBSC collection were 435 out of the 474 who received induction therapy. Of these, 223 were initially randomized to VTD and 212 to TD induction therapy. The median number of collected CD34+ cells was 9.7 × 106/Kg in the VTD arm and 10.7 × 106/Kg in the TD arm (p= n.s.). The planned yield of 4 × 106 CD34+ cells/Kg was achieved with a single harvest in more than 90% of patients in both treatment groups (96% in VTD and 92% in TD, p= n.s.). A yield of CD34+ cells >10 × 106 /Kg was reported in 51% and 56% of patients treated with VTD and TD, respectively (p= n.s.). Only 5 patients (2%) in VTD group and 2 patients (1%) in the TD arm failed to collect more than 2 × 106 CD34+ cells/Kg (p= n.s.). The majority of patients (86% in VTD and 82% in TD, p=n.s.) received CTX as an in-patient procedure, the median time of hospitalization being 4 days. Less than 5% of patients developed grade 3–4 infectious complications (2% in the VTD group vs 3% in TD, p=n.s.) which required hospitalization in only 2 patients. Following ASCT, no significant difference was observed between the two treatment arms in terms of hematologic recovery and non hematological toxicity. Kaplan-Meier curves of TTP and PFS were almost superimposable for patients with a CD34+ yield >10 × 106/Kg and in the range between 4 and 10 × 106/Kg (group 1). These curves were very similar also for patients who collected between 2 and 4 × 106/Kg CD34+ cells or <2 × 106/Kg (group 2). These two groups had significantly different clinical outcomes. Indeed, the 40-month estimates of TTP and PFS were 75% for group 1 vs 40% for group 2 and 60% vs 25%, respectively. OS at 40 months for patients with >10 × 106/Kg CD34+ cells was in the 90% range, a value significantly better than what was seen in the remaining subgroups. In a multivariate Cox regression analysis, yields of CD34+ cells >10 × 106/Kg and in the range of 4 to 10 × 106/Kg were independently associated with prolonged PFS (p=0.001 and =0.027, respectively), while CD34+ cells >10 × 106/Kg predicted for extended OS (p=0.002). Absence of t(4;14) and/or del(17q), and ISS stage 1 or 2 were additional favorable prognostic factors for both PFS and OS, while randomization to VTD independently predicted for longer PFS. Conclusions: Results of the present analysis showed that both TD and VTD shared the advantage of no adverse impact on PBSC collection and the engraftment potential of collected PBSCs. The target for CD34+ cell collection (>4 × 106/Kg) was achieved with a single harvest in more than 90% of patients in both treated groups and a collection failure was reported in 1% to 2% of patients. These favorable results are due to early PBSC collection, which was performed after 3 cycles of TD and VTD, and use of CTX plus G-CSF which allows better stem cell collection and less likelihood of a collection failure. Of particular note, both VTD and TD were associated with a 50% to 59% probability to collect >10 × 106 CD34+ cells/Kg, a variable independently associated with extended PFS and OS. Disclosures: Off Label Use: bortezomib and thalidomide used as induction therapy for newly diagnosed multiple myeloma patients. Baccarani:Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Cavo:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Genzyme: Honoraria.

Impact of Complete Response on Survival with Either Autologous Stem Cell Transplantation or Conventional Chemotherapy: Results of a Pooled Analysis of 5 Phase III Trials in Newly Diagnosed Multiple Myeloma Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 927-927
Author(s):  
Roberto Mina ◽  
Alessandra Larocca ◽  
Massimo Offidani ◽  
Sara Bringhen ◽  
Tommaso Caravita ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Elderly Patients ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Phase Iii ◽  
Conventional Chemotherapy ◽  
Advisory Committees ◽  
The Impact

Abstract Introduction The introduction of novel agents in the treatment of Multiple Myeloma (MM) led to a significant improvement in the quality of response, increasing the number of patients able to achieve a complete response (CR). Several studies showed that the achievement of CR improved survival, both in young and elderly patients with newly diagnosed MM (NDMM). In this study we investigated the impact of CR on survival obtained with either autologous stem cell transplantation or conventional chemotherapy in NDMM patients. Patients and Methods Data from NDMM patientsenrolled in 5 phase III Italian trials were analysed. Three trials included patients eligible for autologous stem cell transplantation (ASCT): RV-MM-209 (melphalan-prednisone-lenalidomide [MPR] vs high-dose melphalan [Mel200] and ASCT, followed by lenalidomide maintenance vs no maintenance), RV-MM-EMN-441 (cyclophosphamide-lenalidomide-dexamethasone vs Mel200-ASCT, followed by lenalidomide [R] versus lenalidomide-prednisone [RP] maintenance) and MM-BO2005 (bortezomib-thalidomide-dexamethasone vs thalidomide-dexamethasone as induction/consolidation, followed by dexamethasone maintenance). The two remaining studies included elderly patients ineligible for ASCT: GIMEMA-MM0305 (bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance vs bortezomib-melphalan-prednisone) and EMN01 (MPR vs cyclophosphamide-prednisone-lenalidomide vs lenalidomide-dexamethasone, followed by R vs RP maintenance). The primary objective of the study was the evaluation of the impact of CR on overall-survival (OS) and progression-free survival (PFS) and its relationship with age (young vs elderly patients) and type of treatment (ASCT vs conventional chemotherapy [CC])). Univariate and multivariate analyses of OS and PFS, including ISS, ASCT and type of novel agents used as induction treatment, were performed. Response was treated as a time-dependent variable. A landmark analysis was performed. Results 2439 NDMM patients were evaluated; the best response was available in 2359 patients. 656 patients achieved a CR or better, whereas 1353 patients achieved a very good partial response (VGPR) or a partial response (PR), and were included in the analysis. After a median follow-up of 44 months, the 5-year OS was 75% in CR patients as compared with 60% in VGPR/PR patients (HR 0.49, p<0.001), and 5-year PFS was 44% and 22% (HR 0.44, p<0.001), respectively. Among CR patients, 383 were treated with ASCT and 273 with CC. A trend towards a better 5-year OS was reported in the ASCT group as compared with the CC group (79% vs 69%; HR 0.6, p=0.09; Figure 1). A significant PFS advantage was observed among CR patients treated with ASCT in comparison with those who received CC (median, 59 vs 47 months; HR 0.54, p=0.008; Figure 2). No significant differences were observed between young and elderly CR patients treated with CC in terms of 5-year PFS (43% vs 41%; HR 0.9, p=0.5) and 5-year OS (73% vs 69%; HR 1.07, p=0.8). In the multivariate analysis, ASCT confirmed to be an independent predictor of prolonged PFS in CR patients, with a trend towards longer OS, in comparison with CC. Conclusions ASCT induced deeper CR that translated into prolonged PFS and OS as compared with CC. No differences were noticed between young and elderly patients achieving a CR with CC. Disclosures Off Label Use: Use off-label of drugs for the dose and/or schedule and/or association. Larocca:Janssen-Cilag, Celgene: Honoraria. Offidani:Janssen-Cilag, Celgene, Sanofi, Amgen, Mundipharma: Honoraria. Bringhen:Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy; Janssen-Cilag, Celgene, Novartis: Honoraria. Caravita:Celgene: Honoraria. Di Raimondo:Janssen-Cilag, Celgene: Honoraria. Gaidano:Celgene: Research Funding; Morphosys, Roche, Novartis, GlaxoSmith Kline, Amgen, Janssen, Karyopharm: Honoraria, Other: Advisory Boards. Petrucci:Celgene, Janssen-Cilag, Sanofi, Bristol-Myers Squibb: Honoraria. Ria:Italfarmaco: Honoraria; Novartis: Honoraria; Janssen-Cilag: Honoraria; Celgene: Honoraria. Hajek:Celgene, Amgen: Consultancy, Honoraria; Janssen-Cilag: Honoraria. Cavo:Janssen-Cilag, Celgene, Amgen, BMS: Honoraria. Boccadoro:Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees. Palumbo:Novartis, Sanofi Aventis: Honoraria; Celgene, Millennium Pharmaceuticals, Amgen, Bristol-Myers Squibb, Genmab, Janssen-Cilag, Onyx Pharmaceuticals: Consultancy, Honoraria.

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