Real-World Outcomes of Ixazomib in the Treatment of Multiple Myeloma from a Single Center in China

OBJECTIVE:To review the role of ixazomib in the treatment of MM from a single center in China, focusing on the efficacy and safety of this oral PI at all stages of disease since ixazomib was approved by CFDA in 2018.METHODS:The data of real-world outcomes were collected from of the patients with high-risk multiple myeloma diagnosed in the blood diseases hospital,CAMS&PUMC from July 2018 to June 2019 when the patients received the first Ixazomib cycle. The patients were divided into three groups, which were salvage therapy of R/RMM, maintenance and frontline therapy of NDMM respectively.RESULTS:The first group was Ixa-based salvage treatment in R/RMM.31 patients were included and median age was 62years(47-71).The proportion of patients with cytogenetic high risk was 50%(One patient was unable to stratify risk). Extramedullary invasion was very high 40% in early relapse. Half of them received more than 2 lines of treatment, and about 10% received 4 or more lines of prior treatment. ORR was 51.6%; ≥ PR 35.5%; VGPR+CR9.7%.The median ixazomib therapy cycles were 3(1-12). 5 patients entered maintenance therapy for more than eight cycles.In all 8 patients who interruptedIxazomib treatment,six were due to disease progression,one was SD,and the remaining one will receive CART therapy.The median follow-up was 6.8 months, and the median PFS was not yet achieved.The survival curves of high-risk group and standard-risk group were obviously separated, but there was no statistical difference.However, the prognosis of extramedullary invasion group was very poor. PFS was significantly shorter than that of control group after treatment with Ixazomib(2.86m vs NA).The second group was Ixa-based maintenance therapy of NDMM. Seven patients received maintenance therapy after ASCT, and 20 transplant-ineligible(TIE) patients entered maintenance therapy.Maitenance with Ixazomib appears to have efficacy with deepen responses,the transplantation group(57.1%CR before vs 85.7%after) similar to the non-transplantation group(35.3%before vs 58.8%after).All the patients did not interrupt Ixazomib treatment.Only 1 patient(3.7%) had grade 4 adverse events, which was thrombocytopenia.The median ixazomib therapy cycles were 4(1-11).The third group was Ixa-based frontline therapy. The median age of 24 patients was 66y (42-79), CA High Risk was 25% (6/24), R-ISS III Stage was 12.5%(3/24), and no patients with EMD.The total of 9 patients were suitable for transplantation. Among them, 5 patients completed stem cell collection, 3 patients completed autotransplantation, 1 patient waited for transplantation, and 1 patient entered the continuous treatment group because of poor mobilization.The other 4 patients were still in induction stage. There were 15 patients in the TIE group and one patient dropped out of the group because of disease progression.The remaining 23 patients achieved a overall response rate of 78.3%. Nearly half of the patients achieved deep remission(VGPR+CR 43.5%).Posttransplantation patients could achieve 100% deep remission rate.As the number of treatment cycles increased, the proportion of complete remission increased in TIE patients.CONCLUSION:Ixazomib as induction/consolidation after ASCT, followed by maintenance, is well tolerated, convenient, and effective. Ixazomib is an important option for high-risk patients with real-world experience.KEYWORDS:Real-world, Ixazomib, multiple myeloma Figure Disclosures No relevant conflicts of interest to declare.

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Patient-reported experience platform identifies discordance between guidelines and real-world practice: Maintenance therapy for high-risk multiple myeloma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e20022 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e20022-e20022

Author(s):

Nathan W. Sweeney ◽

Scott Ryan Goldsmith ◽

Zachary Crees ◽

Thomas H. Molina ◽

Jenny Ahlstrom

Keyword(s):

Multiple Myeloma ◽

Quality Improvement ◽

High Risk ◽

Maintenance Therapy ◽

Real World ◽

Critical Role ◽

High Yield ◽

Patient Portal ◽

Patient Reported ◽

Reported Data

e20022 Background: Patient-reported data play a critical role in assessing clinical benefit from therapeutic interventions and are increasingly used in clinical trials. Internet-based platforms such as HealthTree Cure Hub for Multiple Myeloma ( www.healthtree.org ) provide the opportunity to obtain such real-world patient-reported data, while also providing valuable insights into high-yield areas to focus on quality-improvement efforts. For example, proteasome inhibitor (PI)-based maintenance after autologous stem cell transplantation (ASCT) is a consensus recommendation in many practice guidelines for high-risk multiple myeloma (MM) yet real-world adherence to this practice remains uncertain (PMID 23541011, 30932732). Methods: We examined post-ASCT maintenance therapy in patients with high-risk MM, as defined per mSMART criteria, using patient-reported treatment data from the HealthTree Cure Hub for Multiple Myeloma database. Patients who received an ASCT prior to 2014 were excluded. Results: Our analysis identified 110 MM patients with high-risk MM. Of those, only 48 (44%) received PI-based maintenance therapy. Additionally, 60 (55%) received IMiD (immunomodulatory imide drug) maintenance, 1 (< 1%) received ‘other’, and 1 (< 1%) did not report maintenance therapy. Conclusions: The benefits of PI-based maintenance in MM are well established for high-risk MM. However, analysis of patient-reported data using an online patient portal, HealthTree Cure Hub for Multiple Myeloma, suggests a disparity between practice recommendations and real-world practice patterns. These findings, and others from online patient portals, can serve as a springboard in helping investigators to identify areas for quality-improvement initiatives.

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Real-World Retrospective Study of 46 Patients with Macrofocal Multiple Myeloma (MFMM)

Blood ◽

10.1182/blood-2021-149464 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3765-3765

Author(s):

Wenqiang Yan ◽

Huishou Fan ◽

Jingyu Xu ◽

Jiahui Liu ◽

Chenxing Du ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Retrospective Study ◽

Real World ◽

Working Group ◽

Clinical Characteristics ◽

Conflicts Of Interest ◽

Young Patients ◽

Control Group ◽

Lytic Lesions

Abstract Real-world retrospective study of 46 patients with Macrofocal multiple myeloma (MFMM) Introduction: Multiple myeloma is a clonal plasma cell malignant neoplasm characterized by bone disease and marrow involvement. However, we found that some myeloma patients presented multiple lytic lesions, but didn't meet the diagnostic criteria of at least 10% clonal plasma cells in the bone marrow. And these patients were always diagnosed with myeloma by biopsy-proven plasmacytomas. This special myeloma entity has been called macrofocal multiple myeloma (MFMM) [1-2]. Considering that the data of this rare myeloma entity are limited, it is of great significance to investigate the clinical characteristics, genetic abnormality, treatment response and prognosis of MFMM patients. Methods: Based on the definition (BMPCs<20% and multiple lytic lesions/plasmacytomas, without anemia, renal insufficiency or hypercalcemia) [3]，we identified 46 MFMM patients among 791 myeloma patients(5.8%) diagnosed at out hospital between January 2013 and December 2019. In the same period with same therapies, other 92 typical myeloma patients were selected as the control group. Results: Patient characteristics and comparisons between MFMM patients and the control group are depicted in Table 1. Of the 46 MFMM patients, 82.6% were <65 years and 73.9% had at least 4 lytic lesions. And the incidence of plasmacytomas in MFMM patients was significantly higher than the control group (43.5% vs 18.5%, p<0.05). According to the international staging (ISS) and the Revised ISS, advanced stage patients in the MFMM group was less common than controls (p<0.05). Regarding to the cytogenetics, the high-risk features was infrequent in patients with MFMM compared to typical myeloma patients (15.8% vs 32.2%, p=0.058). And t (11;14) could be observed in 32.4% MFMM patients and 9.4% myeloma patients (p<0.05). The treatment patterns of the two groups were similar; about 30% of the patients received ASCT, and 80% patients received proteasome-inhibitors based regimen as the induction therapy. Concerning about the best response to treatment, the CR rate of the MFMM group was significantly higher than the controls (78.2% vs 60.8%, p<0.05). As of June 2021, the median follow-up time was 37.9 months. The median progression-free survival in the study and control groups were 77.5 vs 39.8 months, respectively (p<0.05). The overall survival (OS) of MFMM patients was significantly longer than typical myeloma patients during the same period with similar therapies (not reached vs 68.2m, p<0.05). Conclusion: In conclusion, Macrofocal multiple myeloma is a special entity of MM, which is characterized with multiple lytic lesions, more extramedullary diseases, less bone marrow infiltration, and fewer adverse features. And the MFMM patient could achieve deep remission and prolonged OS in the era of novel agents. References: [1] Dimopoulos MA, Pouli A, Anagnostopoulos A, et al. Macrofocal multiple myeloma in young patients: a distinct entity with favorable prognosis. Leuk Lymphoma. 2006;47(8):1553-1556. [2] Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538-e548. [3] Katodritou E, Kastritis E, Gatt M, et al. Real-world data on incidence, clinical characteristics and outcome of patients with macrofocal multiple myeloma (MFMM) in the era of novel therapies: A study of the Greco-Israeli collaborative myeloma working group. Am J Hematol. 2020;95(5):465-471. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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

Blood ◽

10.1182/blood-2020-143173 ◽

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.

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Evolving Real-World Treatment Patterns in Patients with Newly-Diagnosed Multiple Myeloma (NDMM) in the United States (U.S.)

Blood ◽

10.1182/blood-2019-124301 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3164-3164

Author(s):

Sikander Ailawadhi ◽

Dorothy Romanus ◽

Dasha Cherepanov ◽

Yu Yin ◽

Meng-Ru Cheng ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Research Funding ◽

Risk Group ◽

Treatment Patterns ◽

Frontline Therapy ◽

Early Cohort ◽

Recent Cohort ◽

The U.S ◽

Over Time

Background Multiple myeloma (MM), a malignant neoplasm of plasma cells in the bone marrow, accounts for up to 1.8% of all cancers in the U.S., most frequently affecting people 65-74 years old. A variety of therapies are available to manage MM, including stem cell transplantation (SCT), immunomodulatory drugs (IMiD), proteasome inhibitors (PI), monoclonal antibodies (mAB), and alkylating agents (alk). Given the heterogeneity of MM and the rapidly evolving therapeutic landscape, MM contemporaneous real-world treatment patterns are not well described. We examined the patient characteristics and first-line (LT1) treatment patterns in NDMM patients. Methods MM patients (≥18 years), diagnosed in April 30, 2015 - April 29, 2017 (early cohort) or in April 30, 2017 - April 30, 2019 (recent cohort), were followed retrospectively from MM diagnosis to last patient activity in the Flatiron Health database - a geographically-diverse, longitudinal electronic health record spanning over 280 community and academic cancer clinics in the U.S. LT1 regimens were described as: 1) containing an IMiD (thalidomide, lenalidomide [R], or pomalidomide), PI (bortezomib [V], carfilzomib, or ixazomib), alk (melphalan, cyclophosphamide [C], bendamustine), mAB (daratumumab, elotuzumab), or combinations of these; and 2) doublet/monotherapy (doublets-) vs. triplet or greater agent (triplets+) combinations. Treatment patterns were examined by SCT status and by cytogenetic risk (high: del17p, t(4;14) and/or t(14;16); standard: ≥1 cytogenetic tests without high cytogenetic risk) and age groups (<65, 65-74, ≥75). Duration of therapy (DOT) and time to next therapy (TTNT) were estimated using Kaplan-Meier methods in the early cohort with longer follow-up. Results Of 4,070 NDMM patients, 3,433 were non-SCT (nSCT: early cohort: n=1,736; recent cohort: n=1,697) and 637 had SCT (early cohort: n=407; recent cohort: n=230). In nSCT patients, mean age at diagnosis was 70 years (SD: 10); 46% were female; 36% had stage III (699/1916, among non-missing), and 15% (392/2574, among non-missing) had high risk MM (25% had unknown cytogenetics). SCT patients were younger at diagnosis (mean [SD]: 61 years [9]); 44% were female; 25% (117/470, in non-missing) had stage III, and 19% (102/547, in non-missing) had high risk MM (14% had unknown cytogenetics). Overall, proportions with known cytogenetic risk were similar within SCT status cohorts over time but were lower in the SCT group (nSCT early vs. recent cohort: 26% vs. 24% had unknown cytogenetics; and in SCT: 15% vs. 13%, respectively). In nSCT and SCT patients, respectively, most common regimens were VRd (d: dexamethasone; 44% and 58%), Rd (16% and 7%), Vd (13% and 1%), and VCd (12% and 4%). In nSCT patients, the use of VRd increased over time (37% [early cohort] to 51% [recent cohort]), while frontline therapy with Rd/Vd doublets (19% to 14%/16% to 9%) and with VCd (13% to 11%) decreased. In the nSCT recent cohort, VRd (51%) frontline therapy dominated, with a slightly higher proportion of patients in the high-risk group vs. standard and unknown risk receiving VRd (56% vs. 53% and 46%); use of doublet therapy with Rd/Vd was lower in the high risk (12%/5%) vs. standard risk group (14%/9%). Irrespective of age, VRd was the most common frontline regimen in the nSCT recent cohort, albeit its use was lower among patients 75+ years of age (43%) vs. younger patients (54% [<65 years] and 59% [65-74 years]); 75+ year old patients had a higher use of Rd/Vd doublets (19%/15%) vs. <65 (10%/5%) or 65-74 (10%/6%) years of age. Triplets+ were more commonly used than doublets- across all cohorts: 59% vs. 41% (nSCT early cohort); 74% vs. 26% (nSCT recent cohort); and 89% vs. 11% (SCT early cohort); 95% vs. 5% (SCT recent cohort). mAB use in the recent cohort was low: 1.4% nSCT and 2.2% SCT patients. In the nSCT early cohort, the median (95% CI) LT1 DOT was 10 months (9-11) and for TTNT was 14 months (13-16). Conclusions PI/IMiD treatment combinations were most commonly observed in both nSCT and SCT patients, with an increase in use from early (40%) to recent (56%) cohort in nSCT patients. Use of triplets, generally, is on the rise from early (60%) to recent cohorts (74%). LT1 TTNT was lower than has been shown in clinical trials. These findings indicate a notable change in treatment patterns over time in nSCT NDMM patients, highlighting the changing landscape of MM management. Disclosures Ailawadhi: Celgene: Consultancy; Takeda: Consultancy; Cellectar: Research Funding; Amgen: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics: Research Funding. Romanus:Takeda: Employment. Cherepanov:Takeda: Employment. Yin:Takeda: Employment. Cheng:Takeda: Employment. Hari:Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Research Funding; Janssen: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Amgen: Research Funding; Spectrum: Consultancy, Research Funding; Sanofi: Honoraria, Research Funding; Cell Vault: Equity Ownership; AbbVie: Consultancy, Honoraria.

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Ixazomib Based Maintenance Therapy for the Patients with Newly Diagnosed Multiple Myeloma in Real-World Practice

Blood ◽

10.1182/blood-2021-149058 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2718-2718

Author(s):

Liye Zhong ◽

Yongqiang Wei ◽

Baohong Ping ◽

Xin Li ◽

Hongling Peng ◽

...

Keyword(s):

Multiple Myeloma ◽

Maintenance Therapy ◽

Real World ◽

Maintenance Treatment ◽

Group Performance ◽

Conflicts Of Interest ◽

Single Agent ◽

Eastern Cooperative Oncology Group ◽

Phase Iii ◽

Newly Diagnosed

Abstract Background The Phase III TOURMALINE-MM4 Trial demonstrated that the oral proteasome inhibitor, Ixazomib maintenance significantly improved progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) not undergoing ASCT. However, patient recruitment for clinical trials is highly selective so the extent to which study populations represent real-world patients is unclear. Currently, data validating the use of ixazomib maintenance in clinical practice in Chinese landscape is scarce. Methods we conducted a retrospective, observational study of NDMM patients meeting International Myeloma Working Group (IMWG) criteria, who received ixazomib-based maintenance therapy. Data was collected from 26 medical centers in southern China. Enrollment was stratified by risk stage, transplant status and maintenance regimens. The characteristics, toxicities and survival outcomes were recorded. Results We included 105 NDMM patients who received ixazomib-based maintenance treatment. Mean age at diagnosis was 59.82 ± 9.80 years, with 62.9% male patients. MM International Staging System (ISS), stage 3 was the most common with 49.04% of patients; 62.86% had an Eastern Cooperative Oncology Group performance score ≥2, and 81.9% with concomitant diseases. By the end of over 70 months follow-up since initial diagnosis, median PFS was 69.45 (95%CI: 31.42-107.48) months, and median OS was not achieved yet. We explored potential influencing factors of progression at the post-maintenance evaluation with a crude model using logistic regression. Difference in PFS was not statistically significant by status at pre-maintenance response, transplantation, maintenance therapy regimens (single/two/three-agent) and dexamethasone in maintenance regimens (p >0.05). Eight patients (7.62%) had grade≥3 treatment-emergent adverse events (TEAEs); 5.7% discontinued treatment because of TEAEs. Common any-grade TEAEs included fatigue (18.1%), diarrhea (16.19%), and peripheral neuropathy (11.43%). Conclusion Although there are certain differences in maintenance treatment options for newly diagnosed multiple myeloma patients in real-world practice, the results of our retrospective study support that the ixazomib-based maintenance therapy was effective with acceptable toxicity and single-agent ixazomib maintenance provided enough clinical benefit compared to two or three agents. Keywords: multiple myeloma, ixazomib, maintenance therapy, real-world practice Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Maintenance Therapy with Decitabine after Allogeneic Hematopoietic Stem Cell Transplantation to Prevent Relapse of High Risk Acute Myeloid Leukemia

Blood ◽

10.1182/blood-2019-124033 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3306-3306

Author(s):

Yunju Ma ◽

Changju Qu ◽

Haiping Dai ◽

Jia Yin ◽

Zheng Li ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

High Risk ◽

Maintenance Therapy ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Median Number ◽

Control Group ◽

Post Transplantation ◽

Hematopoietic Stem ◽

Acute Myeloid

Background: Relapse remains the main cause of treatment failure post transplantation. Relapse prevention is an important strategy for acute myeloid leukemia (AML) patients. M ethods: We retrospectively analyzed the results of21 high risk AML patients who received a median number of 3 courses (range, 2 - 8) of decitabine (DAC) maintenance treatment (20mg/m2/d ×5d every 3 months for 1 year). Meanwhile, another 63 high risk AML patients without any prophylactic treatment after transplantation were included as a control group for 1:3 pair matched study. Results: With median follow-up of 23 months, 20 out of 21 (95.2%) patients maintained complete molecular remission (CMR) in DAC group, while 35 out of 63 (55.6%) patients maintained CMR in control group. Comparing with control group, the patients of DAC group had higher 3-year overall survival (OS) rates and 3-year leukemia free survival (LFS) rates (92.9% vs 51.8%, P =0.003; 94.1% vs 54.7%, P=0.002 respectively). Moreover, DAC maintenance was well tolerated in all patients and grade 3/4 or 4/4 hematological toxicities were observed in 11 of 21 (52.4%) patients. Conclusion: Our results suggested that DAC maintenance therapy was an effective and safe treatment option to prevent relapse after transplantation for high risk AML patients. Disclosures No relevant conflicts of interest to declare.

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Cohort Analysis of FISH Testing of CD138+ Cells in Relapsed Multiple Myeloma: Implications for Prognosis and Choice of Therapy

Blood ◽

10.1182/blood.v124.21.3399.3399 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3399-3399

Author(s):

Dean Smith ◽

Clemency Stephenson ◽

Anna Lach ◽

Steve Chatters ◽

Helena Kempski ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Conflicts Of Interest ◽

Risk Group ◽

Cohort Analysis ◽

Fish Analysis ◽

Newly Diagnosed ◽

Interphase Fish ◽

Line Of Therapy ◽

Standard Risk

Abstract Introduction: Interphase FISH on CD138-selected bone marrow cells enables genetic risk stratification in newly diagnosed multiple myeloma (MM), however as MM remains incurable, most centres still treat newly diagnosed MM uniformly, utilising the most active regimens available. At relapse an increasing choice of regimens, coupled with co-morbidities and treatment-emergent toxicities, means no uniform approach is possible. Instead, therapy is tailored to disease and patient related risk factors. In this setting, FISH testing may be particularly useful if not done at diagnosis and to identify progression events that may alter prognosis. Aim: To evaluate the outcome of FISH analysis in consecutive patients with relapsed MM undertaken at our centre: success rate, frequency of abnormalities, incidence of progression events and correlation of FISH abnormalities with treatment outcomes. Methods: FISH analysis was performed on 192 samples from 154 relapsed patients (2012-13). Plasma cells were selected using magnetic CD138 MicroBeads and interphase FISH carried out using probes as recommended by the EMN (Ross et al, 2012). If patients had no prior results, a full FISH MM panel was performed, using probes for t(4;14), t(14;16), t(11;14), deletion 17p (17p-), Chr 1 abnormalities (1p-/1q+) and deletion 13q (13q-). If patients had been previously tested for an IgH translocation (Tx), a progression event panel was used: 1p-/1q+, 17p- and 13q-. Patients underwent FISH testing prior to starting the next line of therapy. Results: 79% of samples were successfully analysed, with analysis limited in 16% and failed in 5%. Common reasons for failure were poor quality/aged slides, insufficient material and poor hybridisation. 17% of patients had no cytogenetic abnormality. The most common abnormality was 13q- (43.1%), followed by 1q+ (41.4%), t(11;14) (18.3%), t(4;14) (12.4%), 17p- (12.0%) 1p- (8.9%), and t(14;16) (5.6%) Progression events were more common in t(14;16) and t(4;14) groups. All patients with t(14;16) and 82% with t(4;14) had an additional genetic lesion. Only 21% of patients with t(11;14) and 54% with no IgH Tx had an additional event. 80 patients (51.3%) had prior FISH results and 13 (16.3%) had developed a new abnormality on the later test. In 9 cases the progression event was 17p-, in 2 it was 1q+ and 2 cases developed 17p- and 1q+. The patients developing 1q+ were previously standard risk, so repeat testing altered risk group. Acquisition of 17p- indicates especially poor outcome, thus in all 13 cases repeat FISH analysis altered risk. Among patients with progression events none harboured t(11;14), 8 (64%) had no IgH Tx, 3 had t(14;16) and 2 had t(4;14). FISH results were correlated with clinical outcome. Patients were stratified as having high risk genetics [t(4;14), t(14,16), 17p- in ≥50% cells, 1p-/1q+] or standard risk [t(11;14), normal cytogenetics]. 63 (41%) patients were high risk, 83 (54%) standard risk, with no information available for 8 (5%). Both groups had received a median of 2 prior lines of therapy. Response rates (≥PR) to the next line of therapy were similar (60.4% standard risk vs 56.0% high risk). PFS from time of FISH was significantly longer in the standard risk group (9.8 months vs 5.9, p<0.01) as was OS (not reached vs 17.1 months, p<0.01, Fig. 1). In the high risk group, PFS was significantly longer in patients receiving a proteasome inhibitor (PI) as the next line of treatment versus those receiving other therapies (9.6 months vs 4.6, p=0.01) as was OS (not reached vs 9.7 months, p<0.01, Fig. 2). In the standard risk group, PFS was similar if patients received PI or not (9.5 months PI vs 9.8 other) as was OS (not reached both groups, Fig. 2). Conclusions: FISH analysis on MM patients at relapse was achievable. 74/154 patients had no prior results and a further 13 developed new poor prognostic markers, thus FISH at relapse provided new information in 56% of patients. Progression events were more common in patients harbouring t(4;14) or t(14;16). FISH at relapse was prognostic with high risk abnormalities associated with significantly shorter PFS and OS. The use of PI appeared to abrogate this poor prognosis, suggesting FISH at relapse could be a predictive and prognostic marker. Given the availability of second generation PI and the option of bortezomib re-treatment, results of FISH testing at relapse could directly influence clinical practice. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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Outcomes of Lenalidomide Retreatment with Novel Triplet Regimens in Multiple Myeloma Patients Progressing on Lenalidomide-Based Maintenance Therapy: A Single Center Retrospective Analysis

Blood ◽

10.1182/blood-2019-130537 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3198-3198

Author(s):

Chutima Kunacheewa ◽

Lei Feng ◽

Elisabet E. Manasanch ◽

Qaiser Bashir ◽

Krina K. Patel ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Maintenance Therapy ◽

Retrospective Analysis ◽

Board Of Directors ◽

Research Funding ◽

Maintenance Treatment ◽

Single Center ◽

Advisory Committees ◽

Treatment Groups

INTRODUCTION Several phase 3 randomized studies have validated the use of novel 3-drug regimens with lenalidomide (LEN) and dexamethasone (Rd) in combination with carfilzomib (ASPIRE), elotuzumab (ELOQUENT-2), ixazomib (TOURMALINE-MM1), and daratumumab (POLLUX) in relapsed and/or refractory multiple myeloma (MM) with ≥ 1 line of prior therapy. However, these studies notably excluded patients (pts) who were LEN-refractory since the control arm in these studies received Rd. In practice though, many MM pts at first relapse for which these LEN-based triplets are often utilized are progressing on low-dose LEN maintenance therapy, and their outcomes have not been well characterized in the context of these pivotal trials that excluded such pts. In this single-center retrospective analysis, we report the outcomes of LEN-retreatment with a novel LEN-based triplet in pts progressing on LEN-based maintenance therapy, and compare to a smaller, similar cohort of pts treated with a pomalidomide (POM)-based regimen. METHODS MM pts progressing on LEN-based maintenance therapy between 1/1/2015 and 6/30/2018 at MD Anderson Cancer Center after autologous stem cell transplant (ASCT) who were then treated with a LEN-based triplet or POM-based therapy were eligible for this study. Post-maintenance LEN-based triplet regimens included Rd in combination with bortezomib (VRd), carfilzomib (KRd), elotuzumab (ERd), ixazomib (IRd), and daratumumab (DRd). Disease response and progression were assessed by International Myeloma Working Group response criteria. The Kaplan-Meier method was used to estimate progression free survival (PFS) and overall survival (OS), and cohorts were compared by log-rank test. Pts who had not progressed were censored at the time of last disease evaluation prior to any change in therapy or data cut-off of 6/23/2019. RESULTS A total of 88 pts with a median of 1 prior line of therapy were eligible for the study. Baseline characteristics and prior treatment history are summarized in the Table. 66 pts received a LEN-based triplet, and 22 pts received a POM-based regimen after disease progression on LEN-based maintenance. A similar proportion of pts had high-risk cytogenetics (del 17p, t(4;14), and/or t(14;16)) in the LEN-based (21%) and POM-based (18%) post-maintenance treatment groups. The most common LEN-based maintenance regimens included LEN monotherapy (66%), ixazomib and LEN (14%), and elotuzumab and LEN (10%). Median PFS after ASCT on LEN-based maintenance was 26.0 months, and similar between the LEN-based (25.7 months) and POM-based (29.1 months) post-maintenance treatment groups, suggesting enrichment of pts with early progression on LEN-based maintenance in this analysis. In pts retreated with LEN-based therapy, the median LEN dose increased from 10 mg during maintenance therapy to 25 mg in the post-maintenance regimen. The overall response rate (ORR, ≥ PR) to LEN-based retreatment was 56% (≥ VGPR 33%) and median duration of response (DOR) was 11.7 months (95% CI 9.23 - NA). In comparison, the ORR and DOR with POM-based treatment were 73% (≥ VGPR 41%) and 19 months (95% CI 7.88 - NA), respectively. At a median follow-up time of 20.5 months, median PFS and OS were 13.6 and 40 months, respectively, with LEN-based retreatment versus 21.4 months (P 0.7) and not reached (P 0.6) with POM-based therapy. There was no significant difference in PFS or OS between LEN-based triplet regimens (VRd, KRd, ERd, IRd, and DRd). In the LEN-based retreatment group, high-risk cytogenetics did not significantly impact PFS (10.1 vs. 13.6 months, P 0.9), although OS was worse (22.5 vs. 42.8 months, P 0.003). However, pts who progressed on LEN-based maintenance ≥3 years after ASCT had a significantly better median PFS with LEN-based retreatment compared to pts who progressed <3 years after ASCT (median not reached vs. 9.9 months, P 0.001, Figure). CONCLUSION In pts progressing on LEN-based maintenance therapy, retreatment with a LEN-based novel triplet to maximize LEN dose intensity and synergy with other novel agents can lead to deep and durable responses in select pts, particularly in those with a more indolent disease course and longer (≥3 years) PFS after ASCT. However, ORR and PFS may favor switching to a POM-based regimen over LEN-based retreatment in this patient population, and warrants further investigation in studies evaluating optimal sequencing strategies in relapsed and/or refractory MM. Disclosures Manasanch: Sanofi: Research Funding; Quest Diagnostics: Research Funding; Merck: Research Funding; Skyline Diagnostics: Research Funding; Janssen: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Celgene: Honoraria. Bashir:Imbrium: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; StemLine: Research Funding; Acrotech: Research Funding; Celgene: Research Funding. Patel:Poseida Therapeutics, Cellectis, Abbvie: Research Funding; Oncopeptides, Nektar, Precision Biosciences, BMS: Consultancy; Takeda, Celgene, Janssen: Consultancy, Research Funding. Kaufman:Janssen: Other: travel/lodging, Research Funding. Iyer:Novartis: Research Funding; Genentech/Roche: Research Funding; Bristol-Myers Squibb: Research Funding; Arog: Research Funding; Seattle Genetics, Inc.: Research Funding; Incyte: Research Funding. Thomas:Xencor: Research Funding; BMS: Research Funding; Celgene: Research Funding; Amgen: Research Funding. Orlowski:Poseida Therapeutics, Inc.: Research Funding. Qazilbash:Bioclinical: Consultancy; Amgen: Consultancy, Other: Advisory Board; Autolus: Consultancy; Genzyme: Other: Speaker. Lee:Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Daiichi Sankyo: Research Funding; Amgen: Consultancy, Research Funding; GlaxoSmithKline plc: Research Funding; Sanofi: Consultancy.

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Anamnestic factors that shape reproductive health of women with repeated unsuccessful popygamy in vitro fertilization

HEALTH OF WOMAN ◽

10.15574/hw.2016.114.140 ◽

2016 ◽

pp. 140-143

Author(s):

N.V. Cotsabin ◽

◽

O.M. Makarchuk ◽

Keyword(s):

High Risk ◽

Risk Group ◽

Polycystic Ovary ◽

High Risk Group ◽

Stress Factors ◽

Control Group ◽

Fertilization In Vitro ◽

Infertile Women ◽

Group I

The proportion of patients with multiple unsuccessful attempts of assisted reproductive technology (ART) is about 30% of all patients treated with the use of ART. Women with history of unsuccessful ART attempts - a special category of patients who require emergency attention and a thorough examination at the stage of preparation for superovulation stimulation,the selection of embryos and endometrium preparation for embryo transfer. The objective: to distinguish high-risk group of unsuccessful attempts based on a detailed analysis of anamnestic and clinical data of infertile women with repeated unsuccessful ART attempts that requires more in-depth study of hormonal features, ovarian reserve and condition of the endometrium. Materials and methods. For better understanding of the problem of repeated unsuccessful ART attempts and сreation of efficient infertility treatment algorithms for these couples we conducted a thorough analysis of anamnestic data of three groups of infertile women (105 patients), which were distributed by age: group I – younger than 35, the II group – from 35 to 40, the III group - over 40 years. These groups of patients were compared with each other and with the control group of healthy women (30 persons). Results. Leading stress factors in the percentage three times prevailed in the group of infertile women and had a direct connection with the fact of procedure «fertilization in vitro» and chronic stressors caused by prolonged infertility. Primary infertility was observed significantly more frequent in patients younger than 35 years (p <0.05), secondary infertility - mostly in the second and third experimental groups (p <0.05). Noteworthy significant percentage of wellknown causes of infertility and idiopathic factor in all groups, and the prevalence of tubal-peritoneal factor in the second and third experimental groups, and endocrine dysfunction in the I experimental group. The most common disorder among this category of woman was polycystic ovary syndrome. Frequency of usual miscarriage among patients of I ana II groups was two times higher than in the third group (p <0.05). Among the experimental groups the leading place belongs urinary tract infection, respiratory tract diseases, pathologies of the cardiovascular system. Data of the stratified analysis show an increase likelihood of repeated unsuccessful ART attempts under the influence of constant chronic stress (odds ratio OR=2.06; 95% CI: 0.95–3.17; p<0.05). Conclusions. Among infertile patients with repeated unsuccessful ART attempts must be separated a high risk group of failures. The identity depends on the duration of infertility, female age and leading combination of factors. Key words: repeated unsuccessful ART attempts, anamnesis, infertility, high risk.

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Multiple Myeloma Patients Undergoing Carfilzomib: Development and Validation of a Risk Score for Cardiovascular Adverse Events Prediction

Cancers ◽

10.3390/cancers13071631 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1631

Author(s):

Anna Astarita ◽

Giulia Mingrone ◽

Lorenzo Airale ◽

Fabrizio Vallelonga ◽

Michele Covella ◽

...

Keyword(s):

Blood Pressure ◽

Risk Assessment ◽

Multiple Myeloma ◽

Cardiovascular Risk ◽

High Risk ◽

Adverse Events ◽

Risk Score ◽

Risk Group ◽

High Risk Group ◽

Cardiovascular Risk Assessment

Cardiovascular adverse events (CVAEs) are linked to Carfilzomib (CFZ) therapy in multiple myeloma (MM); however, no validated protocols on cardiovascular risk assessment are available. In this prospective study, the effectiveness of the European Myeloma Network protocol (EMN) in cardiovascular risk assessment was investigated, identifying major predictors of CVAEs. From January 2015 to March 2020, 116 MM patients who had indication for CFZ therapy underwent a baseline evaluation (including blood pressure measurements, echocardiography and arterial stiffness estimation) and were prospectively followed. The median age was 64.53 ± 8.42 years old, 56% male. Five baseline independent predictors of CVAEs were identified: office systolic blood pressure, 24-h blood pressure variability, left ventricular hypertrophy, pulse wave velocity value and global longitudinal strain. The resulting ‘CVAEs risk score’ distinguished a low- and a high-risk group, obtaining a negative predicting value for the high-risk group of 90%. 52 patients (44.9%) experienced one or more CVAEs: 17 (14.7%) had major and 45 (38.7%) had hypertension-related events. In conclusion, CVAEs are frequent and a specific management protocol is crucial. The EMN protocol and the risk score proved to be useful to estimate the baseline risk for CVAEs during CFZ therapy, allowing the identification of higher-risk patients.

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