Treatment Outcomes and Toxicity Profile of Kyprolis in Multiple Myeloma: A Single Institution Experience

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-2
Author(s):  
Richa Thakur ◽  
Nina Kohn ◽  
Monique Hartley-Brown
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
High Risk ◽  
Disease Progression ◽  
Real World ◽  
Cell Transplant ◽  
Single Center ◽  
The Real ◽  
Overall Response ◽  
Increased Risk

Background: Survival outcomes of Multiple Myeloma (MM) patients have significantly increased with recent advances in treatment. In the past decade several agents have been FDA approved due to improvement in the progression-free survival (PFS). Kyprolis is an irreversible proteasome inhibitor (PI) that was first approved in 2012 for treatment of MM. The real-world use of Kyprolis in treatment of MM is important to assess. Aim: The primary objective of this study is to evaluate the real-world outcome in overall response rates (ORR) for MM patients treated with Kyprolis. This was a retrospective study at a single center site in the Northwell Health system, evaluating patients at the Monter Cancer Center. Secondary objectives include determining the PFS, and adverse side effects (ADEs), including cardiovascular and renal toxicities of MM patients treated with Kyprolis at our institution. Methods: We retrospectively analyzed the charts of patients with a known diagnosis of MM who were treated with Kyprolis between January 1, 2013, and December 31, 2018. Baseline patient demographics such as age, gender, MM stage at diagnosis based on the Revised International Staging System (R-ISS) criteria, cytogenetics and fluorescence in situ hybridization (FISH), prior treatment regimens, autologous stem cell transplant (ASCT) were collected. Statistical methods included percentage calculations of baseline characteristics. Time to progression was measured from start of treatment to disease progression. PFS was calculated as a mean from initiation of treatment to the time point when progression was first noticed. Results: We identified 66 patients who fit our criteria of inclusion in this study. The median age was 65 years (Range 48 to 84). Based on the R-ISS staging, 7 (10%) patients were stage I, 28 (42.4%) stage II, and 31 (47.0%) were stage III. Based on cytogenetics 31% of the patients were classified as high risk (defined as having a 13q deletion, t (4,14), del(17p), t (14,16), or gain 1q). There were 32.3% of the patients with hyperploidy. A subset of patients was heavily pretreated with approximately 18.2% receiving more than 4 treatment lines prior to initiation of Kyprolis and 22.7% having received 3 prior lines. 42.4% of patients received 2 prior lines of MM- directed therapy. Prior treatments mainly included immunomodulatory agents (IMiDs) such as Lenalidomide and Proteosome Inhibitors (PIs) such as Bortezomib. Cyclophosphamide in combination with Bortezomib and dexamethasone (CyBorD) was also a frequent pre-treatment regimen. In regards to ASCT, 42.4% of patients had undergone prior ASCT before Kyprolis therapy. The overall response rate was 77.2%, with 6.2% having obtained a complete response (CR) as defined by the International Myeloma Working Group response criteria. Thirty-five (53%) patients terminated Kyprolis due to disease progression or intolerance and underwent a change in their treatment. There were 10 patients (15%) who required ASCT after receiving Kyprolis in the setting of progression of disease. The majority of patients that progressed received Daratumumab (40%) or Pomalidomide (46%). Regarding ADEs, grade 2 hypertension was noted in 14% of all patients, acute renal failure (ARF) in 17% of patients, dyspnea in 25.4%, gastrointestinal (GI) toxicity in 16.3%, and fatigue in 40.8% of patients who received Kyprolis. The median PFS on Kyprolis at this site was 6.96 months. Conclusion: Our study shows that Kyprolis improved PFS in patients with MM. However, these patients are at increased risk for cardiac and renal toxicity. This study varies from published findings of clinical trials. Our patients had a higher percentage of high-risk cytogenetics as compared to those in the ASPIRE trial. About 90% of patients in the ASPIRE study had an ECOG status of 0 or 1, which was better than the average seen in our patient population. These two factors may have contributed to a lower observed PFS than that initially observed in the clinical trials. Second, this is a retrospective single center study, with inherent biases that may result in additional variance. The proportion of grade 2 ADEs were comparable to the frequencies reported in the ASPIRE and ENDEAVOR trials. The toxicities noted in this study reinforce the importance for community oncologists to be aware of these issues. Early prevention and management may impact quality of life, response, or tolerance to Kyprolis therapy. Disclosures No relevant conflicts of interest to declare.

scholarly journals A Single Center Review Evaluating Daratumumab Outcomes in Multiple Myeloma Patients at Monter Cancer Center/Northwell Health Cancer Institute

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-25
Author(s):  
Chung H Chen ◽  
Chung-Shien Lee ◽  
Samrah Ahmad ◽  
Monique Hartley-Brown
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Disease Progression ◽  
Real World ◽  
Time Frame ◽  
Cancer Center ◽  
Published Data ◽  
The Real ◽  
Risk Of Death ◽  
Real World Setting

Multiple myeloma (MM) is a malignant neoplasm of plasma cells in bone marrow. Daratumumab (Dara) is a CD38-directed antibody which is Food and Drug Administration (FDA) approved for treatment of patients with MM. Dara is recommended by the National Comprehensive Cancer Network (NCCN) guidelines, which many community oncologist use as the standard of care guidelines. Therefore, we consider it important to analyze Dara use and effects in the real-world community Oncology clinic setting. We evaluated the survival outcomes, both progression-free survival (PFS) and overall survival (OS), as well as the time to progression (TTP) of MM and common adverse events (ADEs) seen in patients at a single site, Monter Cancer Center in the Northwell Health (NH) system. This is a single group study evaluating outcomes of patients with MM who received Dara at NH. Primary objectives include evaluating OS, defined as time from initiating Dara therapy to time of death from any cause. Secondary objectives include PFS, time from initiation of Dara therapy to documented disease progression. We also plan to evaluate time to next treatment (TTNT), TTP and rate of ADEs within 30 days of initiating Dara. This is a retrospective study of patients with MM who received Dara at Monter Cancer Center, Northwell Health Cancer Institute. Basic demographics; gender, age at diagnosis, body mass index (BMI), and ethnicity, were collected. Treatment information collected included, previous number of therapies, dose of Dara in total and per body weight in kg, number of doses of Dara received. Data was collected using electronic medical records from January 2015 through December 2019. Patient charts were reviewed, collecting data from the time of diagnosis and initiation of Dara to date of last known follow-up, or death. Progression of disease information and initiation of new therapy was collected during this time frame. Standard methods of survival analysis were used to analyze the primary objectives. Kaplan-Meier estimate was used to analyze PFS and OS at 6, 12, 24, and 36 months. TTNT was defined as length of time from the date of initiation of Dara to the date the patient was started on a new therapeutic regimen. TTP was defined as the date the patient started Dara therapy to the date of documentation of disease progression or relapse. Cumulative incidence rates were calculated to determine the rates of incidence of next treatment in the presence of competing risk of death, and rate of ADEs in patients during this time frame. Rate of ADEs were reported with corresponding 95% confidence intervals using a binomial confidence interval. A total of 50 patients were included in the analysis. Baseline demographics are in line with published data, mean age was 68.8 years, with a non-Caucasian predominance of 68% to 32% Caucasian. The gender profile was 42% male. Prior mean number of therapies was 2.9, with a median of 2. Dose of Dara used was in line with the recommended dosing with mean 16.3mg/kg dosing. The mean number of doses received were 17. Similar to prior published data the predominant heavy chain MM phenotype was IgG at 48%. The OS, at 36 months was 54%, where 23 patients (46%) had documented date of death during the 5-year time span reviewed. Thirty-one patients (62%) experienced disease progression (TTP), ranging from 28 to 1047 days from start of Dara treatment, with a median TTP of 317 days. The median PFS was 436 days (95% CI: 334-676 days). There were 46% patients that continued on another line of therapy post Dara , with the TTNT ranging from 25 to 541 days, median 175 days from initial Dara therapy. Among patients who had at least one adverse event, the most frequently occurring pattern was fatigue, pyrexia, and chills at 22%, followed by infusion related reactions at 20%. Dara has shown strong clinical efficacy clinical trials. The patients in clinical trials are often not reflective of real-world clinical patients. This study evaluates patients at a single cancer center in the NH system. The data reinforces the efficacy and tolerability of Dara in the real-world setting. It also depicts the difference in OS, PFS, TTP, TTNT and ADEs in the real-world setting. The data suggests Dara outcomes in community-based oncology centers vary from clinical trial data. However, it does indicate similar improved benefits in OS, PFS and TTNT compared with other retrospective studies at other centers. Further prospective studies would be beneficial in evaluating this real-world impact. Disclosures No relevant conflicts of interest to declare.

scholarly journals The real-world outcomes of multiple myeloma patients treated with daratumumab

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258487
Author(s):  
Agoston Gyula Szabo ◽  
Tobias Wirenfeldt Klausen ◽  
Mette Bøegh Levring ◽  
Birgitte Preiss ◽  
Carsten Helleberg ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Proteasome Inhibitors ◽  
Median Number ◽  
The Real ◽  
Treatment Timing ◽  
Risk Patients ◽  
Standard Risk

Most patients cannot be included in randomized clinical trials. We report real-world outcomes of all Danish patients with multiple myeloma (MM) treated with daratumumab-based regimens until 1 January 2019. Methods Information of 635 patients treated with daratumumab was collected retrospectively and included lines of therapy (LOT), hematologic responses according to the International Myeloma Working Group recommendations, time to next treatment (TNT) and the cause of discontinuation of treatment. Baseline characteristics were acquired from the validated Danish Multiple Myeloma Registry (DMMR). Results Daratumumab was administrated as monotherapy (Da-mono) in 27.7%, in combination with immunomodulatory drugs (Da-IMiD) in 57.3%, in combination with proteasome inhibitors (Da-PI) in 11.2% and in other combinations (Da-other) in 3.8% of patients. The median number of lines of therapy given before daratumumab was 5 for Da-mono, 3 for Da-IMiD, 4 for Da-PI, and 2 for Da-other. In Da-mono, overall response rate (ORR) was 44.9% and median time to next treatment (mTNT) was 4.9 months. In Da-IMiD, ORR was 80.5%, and mTNT was 16.1 months. In Da-PI, OOR was 60.6% and mTNT was 5.3 months. In patients treated with Da-other, OOR was 54,2% and mTNT was 5.6 months. The use of daratumumab in early LOT was associated with longer TNT (p<0.0001). Patients with amplification 1q had outcome comparable to standard risk patients, while patients with t(4;14), t(14;16) or del17p had worse outcome (p = 0.0001). Multivariate analysis indicated that timing of treatment (timing of daratumumab in the sequence of all LOT that the patients received throughout the course of their disease) was the most important factor for outcome (p<0.0001). Conclusion The real-world outcomes of multiple myeloma patients treated with daratumumab are worse than the results of clinical trials. Outcomes achieved with daratumumab were best when daratumumab was used in combination with IMIDs and in early LOT. Patients with high-risk CA had worse outcomes, but patients with amp1q had similar outcomes to standard-risk patients.

scholarly journals Evaluation of Functional and Cytogenetic High-Risk Multiple Myeloma Using Real-World Data

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4093-4093
Author(s):  
Ankit Kansagra ◽  
Eric Hansen ◽  
Andrew J. Belli ◽  
Stefanie Goran ◽  
Ching-Kun Wang
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Disease Progression ◽  
Real World ◽  
Multivariate Analyses ◽  
Rapid Disease Progression ◽  
High Risk Patients ◽  
Risk Patients ◽  
High Risk Populations ◽  
Equity Ownership

Abstract Introduction: Multiple myeloma (MM) is a heterogeneous disease with wide variability in outcomes. The presence of cytogenetic abnormalities in MM is of critical importance for prognosis and risk stratification. However, patients who may or may not have sufficient cytogenetic abnormalities to classify as high-risk can still experience rapid disease progression despite therapy, or functional high risk (FHR) disease. These two high risk cohorts comprise vulnerable subpopulations who have a significant burden of disease, and it is critical that we understand the underlying patient characteristics and optimal treatment sequence. We sought to investigate these two high risk patient populations treated in the contemporary real-world practice setting. Methods: A total of 1719 patients were identified in the COTA real-world database as having been diagnosed with active MM on or after January 1, 2015 and classified as either FHR, cytogenetic high risk (CHR), or both. The COTA real-world database is a USA-based real-world evidence database comprised of longitudinal, Health Insurance Portability and Accountability Act (HIPAA)-compliant, data on the diagnosis, clinical management, and outcomes of patients with cancer. Of the 1719 patients, 1260 were identified to be FHR, defined as relapse &lt;18 months from initial active MM diagnosis. A total of 459 patients were identified as CHR, among which 347 were both FHR and CHR. CHR was defined as a patient having at least one of the following abnormalities: t(4;14), t(14;16), t(14;20), del(17p), 1q gain, or hypoploid. Line of therapy was applied programmatically using an algorithm based on International Myeloma Working Group criteria and clinical guidance. The primary outcome was time to next treatment (TTNT) calculated using the Kaplain Meier method. Univariate and multivariate analyses were conducted to understand predictors of rapid disease progression among high-risk patients. Results: In our real-world population, FHR patients tended to be slightly younger, African American, and treated predominantly in the academic setting (Table 1). First-line (1L) and second-line (2L) treatment patterns by category are shown in Table 2. A lower proportion of FHR patients received 1L immunomodulators as compared to the other high-risk groups, while almost half of the CHR patients received 1L stem cell transplant (SCT). In 2L, among patients not receiving 2L SCT, a higher proportion of CHR patients received a daratumamab-based treatment as compared to FHR (23.2% vs. 12.0%, respectively). We observed a longer median (95% CI) TTNT for high-risk patients receiving 2L daratumamab-based treatment as compared to patients who did not: 8.5 months (6.4-13.0) vs. 6.0 months (5.3-6.9), p=0.07 (Figure 1). Univariate and multivariate analyses showed age at diagnosis (HR: 0.98, CI: 0.97, 0.99), normal cytogenetics (HR: 0.78, CI: 0.63, 0.97), 1L immunomodulator (HR: 0.39, CI: 0.22, 0.69), 1L proteasome inhibitor (HR: 1.4, CI: 1.1, 1.8), and 1L SCT (HR: 0.22, CI: 0.15, 0.32) as significant predictors of rapid disease progression. Conclusions: Our study provides important insights comparing high risk populations with MM treated in the real-world setting. A higher proportion of CHR patients received 1L SCT and this provided the longest 1L TTNT as compared to other treatments. In 2L, among patients not receiving 2L SCT, we observed a trend towards significantly longer TTNT provided by dara-based treatment as compared to non-dara based treatment; however, our TTNT is lower than progression-free survival results observed in pivotal trials. We identified potential underlying differences in our patient populations that may be driving the predictors of rapid disease progression, including 1L SCT eligibility and renal disease, and these will be further investigated in propensity score matched populations. Future research will continue to explore optimal treatment sequences in high-risk populations with multiple myeloma to improve patient outcomes. These data highlight an urgent need to better predict FHR patients at diagnosis and develop clinical trials incorporating novel compounds in high risk patients. Figure 1 Figure 1. Disclosures Hansen: COTA, Inc.: Current Employment. Belli: COTA, Inc.: Current Employment, Other: Equity ownership. Goran: COTA, Inc.: Current Employment. Wang: COTA, Inc.: Current Employment, Other: Equity ownership.

scholarly journals Interval Progression Serves As a Predictor of Adverse Outcomes in Patients with Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3940-3940
Author(s):  
Alicia Bao ◽  
Qiuhong Zhao ◽  
Nidhi Sharma ◽  
Naresh Bumma ◽  
Srinivas Devarakonda ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Disease Progression ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Regression Models ◽  
Competing Risk ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Increased Risk

Abstract Background: Multiple myeloma (MM) remains an incurable disease, but deep, lasting remission can be achieved with induction therapy and autologous stem cell transplant (ASCT). The current ASCT treatment timeline includes a gap between the end of induction and the day of ASCT to permit correct mobilization and collection of stem cells. During this interval, some patients experience increases in their MM markers. We specifically evaluated if patients with interval progression (IP) have different outcomes post-ASCT compared to patients without IP. Methods: We completed a retrospective analysis of 482 patients who underwent ASCT at The Ohio State University Wexner Medical Center between 2011 and 2016. MM labs, including protein electrophoresis with immunofixation and free light chains, were obtained at day of diagnosis, end of induction, and day of ASCT. A 20% increase in the index protein between the end of induction and the day of ASCT was defined as IP. The primary outcomes evaluated were time-to-progression (TTP), progression-free survival (PFS), and overall survival (OS). TTP was defined as time from ASCT to disease progression, treating death without progression as a competing risk. PFS was defined as the time from ASCT until either disease progression or death, while OS was defined as the time from ASCT until death or last follow-up. Poisson regression models with robust variance were used to evaluate the associations between patients' characteristics and IP, while competing risk regression models were used for TTP analysis, and Cox regression models for OS and PFS analysis. Results: 482 patients who underwent ASCT for MM between 2011 and 2016 were studied. The patient population was primarily male (n = 296, 61.4%), Caucasian (n = 420, 87.1%), and had IgG disease (n = 269, 55.8%). MM stage at diagnosis was equally represented. Cytogenetic analysis showed 108 (22.4%) patients with 1q21 amplification, 60 (12.4%) patients with t(11;14) translocation, 33 (6.8%) patients with t(4;14) translocation, and 40 (8.3%) patients with 17p deletion. More than 80% of patients underwent maintenance therapy following ASCT. One hundred and fifty-six (32.3%) patients were defined as having IP. Patients in the IP group were significant more likely to have LC disease (p = 0.0018), but no other patient characteristics varied significantly between the two groups. LC disease (relative risk (RR adj) = 2.12, 95% CI 1.37-3.30, p = 0.001) and deletion 17p (RR adj = 1.62, 95% CI 1.08-2.42, p = 0.02) were associated with increased risk of IP on multivariate analysis (MVA). Five-year PFS rates were 47.2% and 36.8% in the non-IP and IP groups, respectively. Five-year cumulative progression rates were 49.0% in the non-IP group and 57.8% in the IP group. Five-year OS rates were 76.8% in the non-IP group and 69.6% in the IP group. On univariate analysis (UVA), IP correlated with inferior outcomes in both TTP (hazard ratio (HR) = 1.39, p = 0.01) and OS (HR = 1.39, p = 0.04). In agreement with previous literature, other factors independently correlated with inferior TTP and OS outcomes, including MM stage, cytogenetics (amp1q, t(4;14), and del(17p)), and absence of maintenance therapy post-ASCT. On MVA, IP was no longer significantly associated with a shorter TTP (HR = 1.16, p = 0.35), but approached statistical significance in conferring inferior OS (HR = 1.40, p = 0.07). Notably, once deletion 17p was removed from the MVA, the presence of IP once again conferred significantly lower OS (HR = 1.45, 95% CI 1.01-2.07, p = 0.04), suggesting that deletion 17p, which is a significant risk factor for both IP and OS, may mediate the effect of IP. Combined, all data suggest that uncontrolled disease prior to ASCT trends towards worse long-term outcomes. Conclusion: In this study, we report the first data regarding patients who experienced rapid disease progression in the interval between induction therapy and ASCT. These patients have inferior TTP, PFS, and OS, likely due to the presence of LC disease or deletion 17p. IP may provide a valuable predictor of robustness of response to ASCT and prompt the need for additional induction cycles or alternative regimens. This is especially relevant for patients with deletion 17p. Indeed, these data support a prospective study of concepts to improve outcomes for patients with IP prior to ASCT. Disclosures Bumma: Amgen: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Ixazomib and dexamethasone in high risk smoldering multiple myeloma: A clinical and correlative pilot study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8051-8051
Author(s):  
Sham Mailankody ◽  
Meghan Salcedo ◽  
Elizabet Tavitian ◽  
Neha Korde ◽  
Nikoletta Lendvai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Overall Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Pilot Trial ◽  
Progression Free Survival ◽  
Overall Response ◽  
Smoldering Multiple Myeloma ◽  
Increased Risk

8051 Background: Patients with high risk smoldering multiple myeloma (HR-SMM) have an increased risk of progression to multiple myeloma (MM)- median time < 2 years. The standard management of these patients currently is close clinical monitoring; however, randomized trials show longer progression-free and overall survival in in HR-SMM patients treated with the oral immunomodulatory drug lenalidomide. We report the use ixazomib, the first oral proteasome inhibitor, in combination with dexamethasone in the setting of HR-SMM. Because proteasome inhibitors can provide deep clinical responses in patients with MM, we set the pre-specified threshold for efficacy high (overall response rate of ≥75%). Methods: In this single arm pilot trial of ixazomib/dexamethasone, patients received 12 4-week cycles of ixazomib/dexamethasone followed by ixazomib maintenance for 24 cycles. The primary endpoint is best overall response after 12 cycles and second objectives include duration of response, safety, and progression free survival. Results: 14 patients with HR-SMM were enrolled between 06/2016 and 03/2018. The median age is 65 years and 10 (71%) of patients were male. 11 (79%) patients were high-risk by the PETHEMA criteria, 2 (14%) by the Mayo Clinic criteria and 1 (7%) by both. At data cut-off (02/07/2019), patients completed a median of 17 cycles and 10 (71%) are continuing treatment. 4 patients have stopped treatment (2 patients for raise in serum markers without progression to MM, and 1 each for toxicities, and co-morbidities unrelated to treatment). 9 (64%) achieved an objective response (8 PR, and 1 VGPR) and no patient has progressed to MM. Non-heme adverse events included 3 grade 1 GI events, 2 grade 3 lung infection, 1 grade 2 acute kidney injury, and 1 had grade 1 fatigue that was possibly related to treatment. Conclusions: Ixazomib/dexamethasone appears well tolerated with high overall response (9/14; 64%) in patients with HR-SMM. Although the trial does not meet our pre-specified threshold for efficacy (i.e. best overall response rate of 75%), with a median follow-up of 17 months, no patient progressed to MM and only 2 patients had serologic progression. These results support further evaluation of ixazomib/dexamethasone alone and in combination with other agents as treatment for patients with HR-SMM. Clinical trial information: NCT02697383.

scholarly journals Prognostic Value of PET/CT Performed Day +100 Post Autologous Stem Cell Transplantation in Multiple Myeloma: Real-World Single Center Experience

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-7
Author(s):  
Ludmila Muronova ◽  
Martin Havel ◽  
Tereza Popkova ◽  
Hana Plonkova ◽  
Roman Hajek ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Clinical Trials ◽  
Nuclear Medicine ◽  
Stem Cell ◽  
Prognostic Factor ◽  
Stem Cell Transplantation ◽  
Real World ◽  
Single Center ◽  
Pet Ct

Background: Evaluation of minimal residual disease (MRD) in multiple myeloma (MM) has become a standard procedure and has been incorporated to International Myeloma Working Group updated response criteria in 2016. Its value as an important prognostic factor with impact on survival as well as a relevant end-point in clinical trials has been established by many studies. Assessment of MRD inside the bone marrow is performed basically by two standardized techniques: i) next generation flow cytometry (NGF) and ii) next generation sequencing (NGS). Positron emission tomography and computed tomography (PET/CT) is currently considered as a best tool to evaluate MRD outside of the bone marrow. The standard timepoint to assess the MRD by PET/CT in transplant eligible newly diagnosed multiple myeloma (TE NDMM) patients is considered Day +100 post-autologous stem cell transplantation (ASCT) according to largest CASSIOPET study (Moreau et al., Blood, 2019). Nevertheless, this kind of data from real-world outside the clinical trials setting remains limited. Aim: To evaluate the prognostic impact of PET/CT performed on Day +100 post-ASCT in consecutive cohort of real-world TE NDMM patients from a single center in the Czech Republic. Methods: 18 TE NDMM patients with median age of 59 years (range 42 - 71 years), ISS stage III 17% (3/18) diagnosed between September 2017 and June 2019 received proteasome inhibitor plus immunomodulatory drug containing induction. Patients who reached at least very good partial response (VGPR) after ASCT were indicated for MRD evaluation using NGF technique according to standardized EuroFlow protocol with sensitivity to 10e-6 and for PET/CT evaluation - both at Day +100 post-ASCT. For the evaluation of PET/CT scans complex evaluation by nuclear medicine specialist based on Italian Myeloma criteria for PET Use (IMPeTUs) criteria were used (IMPeTUs) criteria were used (Nanni et al., Eur. J. Nucl. Med. Mol. Imaging. 2018). Results: Of 18 evaluated TE NDMM patients (17 in complete remission (CR), 1 in VGPR), there were 78% (14/18) considered PET/CT negative and 22% (4/18) were considered PET/CT positive at Day +100 post-ASCT. Patients who were PET/CT positive had significantly shorter median PFS (mPFS 29 days) versus those who were PET/CT negative (mPFS not reached); p value &lt; 0.001. Calculated median follow-up for the whole cohort was 245 days. Interestingly, one patient who was NGF MRD negative within the bone marrow was considered PET/CT positive and has early relapse after ASCT. Conclusion: We demonstrated on limited number of real-world TE NDMM patients that those who are PET/CT positive at Day +100 post-ASCT have significantly shorter mPFS compared to those who are PET/CT negative. The aim of myeloma community should lead to the implementation of simultaneous assessment of MRD inside the bone marrow in combination with imaging technique (PET/CT) outside the bone marrow, as this combined evaluation seems to be the most important prognostic factor. Moreover, great effort should be make to establish standardized evaluation protocols for nuclear medicine specialists as well as the most appropriate time-points to perform PET/CT, such as Day +100 post-ASCT in TE NDMM. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals Real-World Conditional Survival Analysis of Patients with Relapsed/Refractory Classical Hodgkin's Lymphoma in the US

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 24-25
Author(s):  
Kaushal D Desai ◽  
Xiaoqin Yang ◽  
Adrienne M Gilligan ◽  
Yeran Li ◽  
Monika Raut ◽  
...  
Keyword(s):  
Disease Progression ◽  
Real World ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Cell Transplant ◽  
Conditional Survival ◽  
Publicly Traded ◽  
The Real ◽  
Real World Setting

Introduction:While the majority of patients (pts) with newly diagnosed classical Hodgkin's lymphoma (cHL) achieve remission following first-line therapy, approximately 30-40% will relapse or become refractory (R/R). Despite R/R status, the 5-year relative survival rate in this population is high (ranging from 78% to 92%) (American Cancer Society 2020). While overall survival (OS) is an unambiguous measure of efficacy in clinical trials, using it as a primary end point requires a long duration of follow-up and may prolong the process of identifying novel and potentially beneficial therapy. Surrogate outcomes, such as progression-free survival (PFS) and time to progression (TTP) are sometimes regarded as valid alternatives when assessing efficacy of a treatment in the absence of mature OS data. The objectives of this study were to assess the conditional survival (CS) given prior PFS among R/R cHL pts treated in the real-world setting. Methods:This retrospective cohort study used electronic medical record (EMR) data of US pts from a network of oncology practices, including practices affiliated with CancerLinQ, maintained in the Definitive Oncology Dataset. Eligible adult (≥18 years) pts who had a confirmed diagnosis of cHL and ≥1 R/R event that occurred between 2000 to 2019 were included. Refractory disease was defined as not achieving a complete or partial response (CR or PR) during a line of therapy. Relapsed disease was defined as the reappearance of cHL at any time after the end of treatment after having achieved a CR or PR. PFS and OS were measured from the start of second-line [2L] therapy to the earlier or disease progression or death; pts without evidence of disease progression or death were censored at the last observed visit. The association between PFS and OS was quantified through the nonparametric Kendall tau rank correlation for bivariate censored data. CS was defined as the Kaplan-Meier probability of surviving an additionalymonths (from the start of 2L), given no OS or PFS event in the previousx(&lt; y) months. Results:A total of 286 R/R cHL pts were included. Most pts were Caucasian (77.3%, n=221) with a median age of 35 years (range: 19-86) at the first R/R event. Median length of follow-up was 12 months from the first R/R event. The most common B symptoms reported were night sweats (38.8%, n=111), weight loss (36.4%, n=104), and fatigue (27.3%, n=78). More than half of pts (54.9%, n=157) received autologous stem-cell transplant (SCT) and 6.6% (n=19) received allogenic SCT. Two-hundred twenty-six pts (79.0%) had documented 2L therapy (first R/R event). From the first R/R event, among these 226 pts, median PFS was 21.0 months (95% confidence interval [CI]: 15.1, 52.5) and median OS was 146.7 months (95% CI: 119.9, not achieved [NA]). CS rates among pts alive without disease progression increased with time: 1-year and 6-year survival rates were 95.7% (95% CI: 91.5, 97.8) and 79.3% (95% CI: 70.5, 85.7), respectively, in pts alive without progression at 3 months, but increased to 100.0% (95% CI: 100, 100) and 94.6% (95% CI: 79.9, 98.6) in pts alive without progression at 3-years (Table). The calculated Kendall tau correlation was 0.42 (p&lt;0.0001), which suggested a statistically significant dependence between PFS and OS. Conclusion:In the real-world setting, R/R cHL pts with longer time without disease progression had lower rates of death and better prognosis. Results from this study support a relationship between PFS and OS; however, further validation and acceptance of PFS as a surrogate endpoint in cHL is required. Establishing these relationships may inform future clinical trial design and interpretation of interim trial data. Disclosures Desai: Merck & Co., Inc:Current Employment, Current equity holder in publicly-traded company.Yang:Merck & Co, Inc.:Current Employment.Gilligan:ConcertAI:Current Employment;Merck & Co., Inc.:Research Funding.Li:Merck & Co., Inc.:Current Employment, Current equity holder in publicly-traded company.Raut:Merck & Co., Inc.:Current Employment.Nahar:Merck Sharp & Dohme, Corp., a subsididary of Merck & Co., Inc., Kenlworth, NJ, USA:Current Employment.

scholarly journals Clinical Features and Predictive Factors of Early Mortality in Patients with MM Outside of Clinical Trials

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5593-5593
Author(s):  
Hiroki Kobayashi ◽  
Yoshiaki Abe ◽  
Daisuke Miura ◽  
Kentaro Narita ◽  
Akihiro Kitadate ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
High Risk ◽  
Predictive Factors ◽  
Real World ◽  
Medical Center ◽  
Early Mortality ◽  
Novel Agents ◽  
Predictive Score ◽  
Ecog Ps

Abstract Background Novel agents such as proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) have improved the overall survival of patients with newly diagnosed multiple myeloma (NDMM) over the last decade. However, early mortality (EM) remains a serious obstacle for a portion of the patients despite receiving novel agents. The report based on clinical trials showed that age, International Staging System (ISS), lactate dehydrogenase (LDH) levels, and high-risk cytogenetic abnormalities (CA) predict EM due to myeloma progression. The result, however, may differ from real-world settings because the patients of clinical trials are relatively younger and have fewer health problems, and the major cause of EM is not only disease progression, but also infections and comorbidities. In this study, we retrospectively analyzed the clinical variables that affected EM in patients with multiple myeloma (MM) in the real-world setting in the novel agent era. Patients and Methods The study population consisted of 238 consecutive patients with NDMM between January 2008 and April 2018 at Kameda Medical Center, Japan. All patients were administered PI- or IMiD-based combined chemotherapy in the frontline setting. Patients diagnosed with smoldering MM and solitary plasmacytoma and who did not receive treatment were excluded in this study. Early mortality was defined as death within two years after diagnosis due to any cause. Comorbidities were evaluated according to the Charlson Comorbidity Index (CCI). Instrumental Activities of Daily Living (IADLs) were retrospectively scored based on medical records. IADLs were assessed by the percentage of the score because the full score of IADLs is different between men and women. High-risk CA was defined by the presence of t(4;14), t(14;16), and del(17p). Statistical analyses were performed with EZR, which is a graphical user interface for R ver. 3.2.2. Ethical considerations This study was approved by the institutional review board of Kameda Medical Center and conducted according to the principles of the Declaration of Helsinki. Results The median age of the patients was 72.2 years, and the median observation period was 40.8 months. Fifty patients (21.3%) died within two years. The major causes of mortality were myeloma progression (36%), infection (22%), and comorbidities (20%). Baseline involved free light chain (iFLC), LDH > normal range, and high-risk CA were not statistically significant between the patients with or without EM. There were significant differences in age, reduction in iFLC on day 7 from the baseline, ISS stage, Revised-ISS stage, Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≥3, CCI score ≥4, and the percentage of IADL scores between the two groups (Table1). Next, we analyzed IADL scores and the reduction in iFLC on day 7 because these variables were not assessed in previous studies. Receiver-operating characteristic curve analysis showed that the best cutoff values were 50% for IADL scores and 65% for the reduction in iFLC on day 7. Univariate analysis suggested that the factors associated with EM were age >75 years, ISS stage 3, CCI score ≥4, ECOG-PS ≥3, IADL <50%, and iFLC reduction >65% on day 7. The multivariate analysis showed that CCI score ≥4 [odds ratio (OR), 2.43; 95% confidence interval (CI), 1.11-5.32; p=0.027], IADL score <50% (OR, 3.31; 95% CI, 1.42-7.70; p=0.006), and iFLC reduction >65% on day 7 (OR, 3.20; 95% CI, 1.45-7.07, p=0.004) were independent predictive factors for EM (Table2). Thus, the EM predictive score was established according to following variables: CCI score ≥4, IADL score <50%, iFLC reduction >65% on day 7, and ISS stage 3. Sixty patients were categorized with high scores (score ≥3), and half of the patients with high scores died within two years, while only 10% of the patients with low scores (score <3) died within two years (p<0.001). Conclusion One-fifth of the patients with NDMM died within two years due to myeloma progression, infection, and comorbidities. Our results suggested that high-risk CA and high levels of LDH did not have predictive value for EM in patients with NDMM outside of clinical trials. The presence of high CCI scores, low IADL scores, and decreases in iFLC (>65%) on day 7 from the baseline were independent prognostic factors, which could reflect both patient and disease factors. The combination of the CCI score, IADL score, ISS stage, and early reduction in iFLC may help in the identification of EM. Disclosures No relevant conflicts of interest to declare.

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