Aspirin Use and Survival in Multiple Myeloma Patients

Abstract Background: Multiple myeloma (MM) is a lethal malignancy with 5- and 10-year survival rates of 46.7% and 20.6%, respectively. Marked advancements in treatment have improved survival within the last decade but are expensive and do not achieve cure. It is known that inflammation is important in MM pathogenesis, and regular aspirin use has been shown to confer a reduced risk of incident MM. However, the influence of aspirin on survival after diagnosis of MM is unknown. We investigated this question prospectively in two large cohorts. Methods: We identified 567 men and women diagnosed with MM between 1980 and 2012 in the Health Professionals Follow-up Study (HPFS) and the Nurses' Health Study (NHS). Participants in both cohorts reported aspirin intake biennially on follow-up questionnaires beginning in 1986 in HPFS and 1980 in NHS. Using multivariable Cox proportional hazards regression models, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for MM-specific and overall mortality through 2015 according to aspirin use patterns. We also examined differences in MM clinical characteristics by aspirin use patterns in a subset of participants with available clinical data. Results: After a median follow-up of 40 months, there were 135 total deaths (76%) and 107 MM−specific deaths (60%) among 177 participants who used aspirin after MM diagnosis, compared with 222 total deaths (90%) and 195 MM−specific deaths (79%) among 247 participants who did not use aspirin. Compared with nonusers, participants who used aspirin after diagnosis had a multivariable HR for MM−specific mortality of 0.55 (95% confidence interval [CI], 0.41, 0.73) and for overall mortality of 0.58 (95% CI, 0.45, 0.75), after adjustment for age at diagnosis, year of diagnosis, sex, body mass index, pre-diagnosis aspirin use, and number of comorbidities. We also observed evidence of a dose response association between postdiagnosis aspirin quantity for both MM-specific and overall mortality (P-trend <0.01). The association between postdiagnosis aspirin use and MM-specific and overall mortality were not materially different in models that excluded deaths that occurred within 12 months of completing the postdiagnosis aspirin assessment. We could not adjust for first line therapy, but adjustment for year of diagnosis may partially control for first line therapy in these cohorts. In a subsample (n=225) of participants with clinical data available, we did not observe statistically significant differences in the clinically presenting features of MM by post diagnosis aspirin use. We also did not observe statistically significant associations between pre-diagnosis quantity or duration of aspirin use and MM-specific or overall mortality. Conclusions: Although lack of adjustment for clinical parameters is a limitation, the findings suggest that aspirin use after MM diagnosis is associated with a lower risk of MM−specific and overall mortality. Disclosures Ghobrial: Celgene: Consultancy; BMS: Consultancy; Janssen: Consultancy; Takeda: Consultancy.

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Patterns of Disease Relapse and Progression in Patients with Multiple Myeloma After First Line Therapy with Autologous Stem Cell Transplantation: Implications for Patient Monitoring After Transplantation

Blood ◽

10.1182/blood.v118.21.825.825 ◽

2011 ◽

Vol 118 (21) ◽

pp. 825-825

Author(s):

Dmitriy Zamarin ◽

Manisha Bhutani ◽

Danielle Chimento ◽

Sergio Giralt ◽

Nikoletta Lendvai ◽

...

Keyword(s):

Multiple Myeloma ◽

Soft Tissue ◽

First Line ◽

Post Transplant ◽

First Line Therapy ◽

Line Therapy ◽

Group A ◽

One Year ◽

Group B

Abstract Abstract 825 BACKGROUND: Autologous stem cell transplantation (ASCT) is a widely used therapeutic option in first line treatment of multiple myeloma (MM). However, many patients eventually relapse. While precise knowledge of relapse and progression (R/PD) patterns would be important to generate evidence based surveillance recommendations after ASCT, such data is limited in the literature, especially in the era following the introduction of the free light chain assay. The purpose of this study is to examine the patterns of post-ASCT relapse and to derive evidence based recommendations for optimal surveillance of patients. METHODS: We performed a retrospective analysis on 258 patients with MM who underwent ASCT within one year of diagnosis at MSKCC between 2000 and 2010, as part of first line therapy. We used the IMWG standard criteria for serologic and clinical R/PD. We first determined for all patients the date of serologic R/PD. Patients identified as having serologic R/PD were further examined to determine whether clinical (anemia, renal failure, hypercalcemia, development of soft tissue lesions), radiologic (skeletal survey) or urinary R/PD had anteceded serologic R/PD. Several groups of patients were derived and further analyzed in terms of relapse patterns and adequacy of follow up. RESULTS: Among 258 patients, 173 were determined to have serologic R/PD at a median of 19.2 months post-transplant. Among these patients, on the dates of their serologic R/PD, 17 (9.8%) had concurrent overt symptomatic evidence of clinical/radiologic R/PD (Group A symptomatic R/PD), while 156 (90.2%) were found to have isolated asymptomatic serologic R/PD without apparent evidence of concomitant clinical/radiologic R/PD (Group B asymptomatic R/PD). Group A included patients with distinct and sometimes coinciding clinical characteristics (poor risk cytogenetics with aggressive disease (n=3), leptomeningeal relapse (n=1), soft tissue relapse (n=4) and acute severe anemia at relapse (n=3)); patients with IgA gammopathy (n=5); and patients considered to have inadequate serologic follow up intervals (range of follow up interval between date of serologic R/PD and prior serologic testing 149 to 245 days) (n=6). Upon further examination of group B, 44 patients had radiologic imaging at the time of serologic R/PD (within 4 weeks following the date of serologic R/PD). Fourteen among them (32%) had evidence of new bone lesions. Among all 173 patients with serologic R/PD, 83 patients had a skeletal survey within one year prior to the date of serologic R/PD. Only 3 (3.6%) had evidence of radiologic R/PD anteceding serologic R/PD. All 3 patients were considered to have had inadequate serologic follow up interval (Range 208 to 252 days). Abnormal urine immunofixation (UIF) anteceded serologic R/PD in 5 out of 41 (12%) patients tested who had achieved CR post transplant. In these patients the abnormal UIF anteceded the serologic R/PD by a mean of 2.4 months. Abnormal UPEP anteceded serologic R/PD by 1.9 months in only 1 out of 40 (2.5%) patients tested who had achieved less than CR post transplant. CONCLUSIONS: Based on the results of this analysis, several conclusions can be drawn: 1) The vast majority of R/PD in patients with MM are asymptomatic R/PD detected first by serologic studies. A small percentage of patients (those with aggressive cytogenetics, specific relapse types including soft tissue, severe cytopenia, and IgA gammopathy) will have symptomatic R/PD with overt concomitant evidence of clinical and/or radiologic R/PD at the time of serologic R/PD; 2) Among patients who have apparent asymptomatic R/PD, a significant percentage will have evidence of skeletal lesions and therefore imaging should be recommended in these patients; 3) In the absence of serological R/PD, routine surveillance screening with yearly skeletal surveys cannot be recommended based on this analysis since this test was not useful in any of the analyzable patients in whom it was obtained; 4) Aside from few patients in CR whose relapse may be detected earlier by UIF (with probably no clinical benefit), all patients with multiple myeloma whose disease progresses will have serologic R/PD at the time of progression and follow up limited to serologic testing may well be sufficient for monitoring patients with MM post transplant. Disclosures: No relevant conflicts of interest to declare.

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Clinical Experience Of Lenalidomide Plus Low Dose Dexamethasone As First-Line Therapy For Multiple Myeloma At a Large County Hospital Caring For An Indigent Population

Blood ◽

10.1182/blood.v122.21.5399.5399 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5399-5399

Author(s):

Yehuda E. Deutsch ◽

Daniel J Dammrich ◽

Jesus C Fabregas ◽

Agustin Pimentel ◽

Alexandra Stefanovic ◽

...

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

Real World ◽

Patient Population ◽

County Hospital ◽

Published Data ◽

First Line ◽

First Line Therapy ◽

Line Therapy

Abstract Background There is ample data for the response rates and clinical outcomes for patients with newly diagnosed multiple myeloma (MM) treated with first-line lenalidomide and dexamethasone (LEN/DEX). Phase II and III studies have reported objective response rates (ORR) in the range of 70-90%. However, extrapolating from clinical trials to ‘real world' clinical practice is sometimes difficult. This is particularly so when it comes to large city hospital systems such as Jackson Memorial Hospital (JMH) in Miami, Florida. JMH is the third-largest public hospital and third-largest teaching hospital in the United States. Patients are primarily uninsured or insured through Medicaid. Additionally, one might surmise, that for a medication like LEN- with a relatively narrow therapeutic index, high cost, and cumbersome prescribing/dispensing requirements- outcomes in the ‘real world' might be inferior to those cited in clinical study. We endeavored to explore such outcomes in JMH to determine whether the benefits of this high cost drug in this setting are concordant with published data. Methods We conducted a retrospective analysis of all patients enrolled into the Celgene patient assistance program and prescribed LEN from January 1, 2010 through July 30, 2013 at JMH. We identified 96 patients enrolled into this program, 35 patients received LEN/DEX as first-line therapy for MM and are evaluable for this analysis. The primary end-point for analysis was response at 4 months. Results Medical records of 35 patients were reviewed. The mean age was 59 (46-75), majority of patients were female (60%), and 29% were black. Consistent with our patient population, 71.4% of patients were Hispanic, 44% were uninsured, and 64% had Medicaid. IgG (60%) was the most common heavy chain involved while 3 patients had light chain disease only. The majority of patients (88.6%) had stage III disease by the Durie-Salmon criteria, and 37.1% had ISS stage III disease. Cytogenetic studies were evaluable in 30 patients: 66.7% were standard-risk, 30% intermediate-risk and 3.3 % high-risk according to mSMART risk classification. At 4-month follow-up, 26 (74.3%) patients had an OR: 6 (17.1%) patients had CR, 7 (20%) had VGPR, and 13 (37.1%) had PR. 6 (17.1%) patients had progressive disease, change in therapy, or were lost to follow-up. There were no documented deep venous thromboses, a known risk of LEN therapy. Only 8 patients (23%) underwent autologous stem cell transplant following primary therapy. Conclusion Responses with upfront LEN/DEX in MM at JMH, were relatively similar to published data in large clinical studies. This provides support for the extrapolation of data from well supported clinical trials at fully-resourced medical institutions, for an oral chemotherapy drug with significant potential toxicities and logistical barriers, to a primarily Medicaid patient population in a county hospital. Disclosures: No relevant conflicts of interest to declare.

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Updated Report of T-Bird (thalidomide, clarithromycin/[Biaxin®], lenalidomide/[Revlimid®], Dexamethasone) Therapy for Upfront Use In Symptomatic Multiple Myeloma

Blood ◽

10.1182/blood.v116.21.3050.3050 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3050-3050

Author(s):

Tomer M Mark ◽

Jennifer O'Loughlin ◽

Morton Coleman ◽

David Jayabalan ◽

Roger N Pearse ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Skin Rash ◽

Complete Response ◽

First Line ◽

Free Survival ◽

First Line Therapy ◽

Line Therapy ◽

Dexamethasone Therapy

Abstract Abstract 3050 Background: We hypothesized that the addition of thalidomide to BiRD therapy (clarithromycin/[Biaxin®], lenalidomide/[Revlimid®], dexamethasone) may improve the anti-myeloma activity of the combination while not adding to overall regimen toxicity, given the different side effect profiles of thalidomide and lenalidomide. We now report an update of the phase 2 trial of T-BiRD (thalidomide/Thalomid®, clarithromycin/[Biaxin®], lenalidomide/[Revlimid®], dexamethasone) therapy for use in up-front treatment of symptomatic multiple myeloma (MM). Methods: Twenty-six patients with newly-diagnosed symptomatic MM were enrolled in a single-institution trial of T-BiRD. The T-BiRD regimen consists of clarithromycin 500mg twice daily, dexamethasone 40mg on days 1,8,15,22 of a 28-day cycle, and lenalidomide 25mg for days 1–21 of a 28-day cycle. Thalidomide is given at a dose of 50mg daily for the first week and thereafter at 100mg daily. All subjects had thromboprophylaxis with aspirin, 162 mg once weekly, 81mg on subsequent days throughout all treatment. Serum protein electrophoresis/immunofixation as well as free light chain determinations were done monthly. Bone marrow biopsy and skeletal imaging were done to confirm disease progression or complete response (CR). Results: Twenty-five patients had completed at least one cycle of T-BiRD and were evaluable. The median number of T-BiRD cycles was 5 (range 1–12). Response to T-BiRD, audited at time of autologous stem cell transplantation (ASCT) or other planned change in therapy, was: 1 (4%) progression of disease (PD), 4 (16%) stable disease (SD), 10 (40%) partial response (PR), 8 (32%) very good PR (VGPR), 1 (4%) complete response (CR), and 1 (4%) with unconfirmed CR, giving a overall response rate (ORR; 3PR) of 80% and a 3VGPR rate of 40%. Nine subjects subsequently underwent ASCT as part of a first line of therapy with T-BiRD induction. These subjects had an ORR of 100% to first-line therapy, with 2 maintaining PR (22%) 5 achieving VGPR (56%), and 2 achieving CR (22%). At three years of follow-up, median progression free survival (PFS) and event free survival (EFS) was not reached for first line therapy (median PFS and EFS censoring at time of ASCT were 65 and 53 weeks, respectively). Median overall survival (OS) was not reached; at 3-year follow-up, 2 patients had died of progressive myeloma, giving an overall survival rate of 92%. A total of 12 subjects (48%) experienced an adverse event (AE), 5 (20%) being study-drug related (RAE). Eight subjects (32%) withdrew from the study: 2 had grade 2 skin rash prior to initiation of full-dose thalidomide (RAE), 1 patient had grade 4 skin rash (Stevens-Johnsons syndrome, SJS) during cycle 1 (RAE), 1 had a TIA in cycle 2, 1 developed renal failure in cycle 1, 1 developed chest pain in cycle 3. Other toxicities include 1 patient with Grade 2 steroid myopathy (RAE), 1 patient with DVT of the leg (RAE), and 1 patient with atrial fibrillation. 2 subjects developed pneumonia (causitive organism not identified). 1 subject died of progressive myeloma prior to completion of 1 cycle. Conclusions: T-BiRD has promising activity as an induction regimen as part of first-line therapy for MM, with prolonged responses; however, toxicity limited extended use. T-BiRD does not appear to be superior to BiRD in ORR, likely due to shorter average time of regimen exposure (median 5 cycles of T-BiRD versus 13 cycles of BiRD). These data continue to support the role of lenalidomide-based regimens in the upfront treatment of MM. Disclosures: Mark: Celgene Corp: Speakers Bureau. Off Label Use: Lenalidomide - upfront use in myeloma. Coleman:Celgene Corp: Speakers Bureau. Zafar:Celgene Corp: Speakers Bureau. Leonard:BiogenIDEC: Consultancy; Genentech: Consultancy; Immunomedics: Consultancy. Niesvizky:Celgene Corp: Consultancy, Speakers Bureau.

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Superiority of Double over Single Autologous Stem Cell Transplantation as First-Line Therapy for Multiple Myeloma.

Blood ◽

10.1182/blood.v104.11.536.536 ◽

2004 ◽

Vol 104 (11) ◽

pp. 536-536 ◽

Cited By ~ 10

Author(s):

Michele Cavo ◽

Claudia Cellini ◽

Elena Zamagni ◽

Patrizia Tosi ◽

Delia Cangini ◽

...

Keyword(s):

Multiple Myeloma ◽

Complete Remission ◽

Autologous Transplantation ◽

High Dose ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Significant Difference ◽

The Impact

Abstract The “Bologna 96” clinical trial was designed in an attempt to prospectively compare a single autologous transplantation (Tx-1) versus double autologous transplantation (Tx-2) as part of first-line therapy for patients with symptomatic multiple myeloma (MM) and less than 60 years of age. Tx-1 was given to support melphalan 200 mg/m2 (MEL-200); Tx-2 was given to support a first course of MEL-200 followed, within 3 to 6 months, by melphalan 120 mg/m2 + busulfan 12 mg/kg. In both arms of the study, autologous transplantation was preceded by 4 courses of VAD and subsequent collection of peripheral blood stem cells with high-dose cyclophosphamide 7 g/m2. An analysis was performed using an intent-to-treat approach on 228 patients who were randomly assigned to Tx-1 (n=115 patients, median follow-up of living patients: 45 months) or Tx-2 (n=113 patients, median follow-up of living patients: 54 months). In comparison with Tx-1, Tx-2 prolonged event-free survival (EFS) of 12 months (P=0.001) and time to progression (TTP) of 17 months (P=0.0001). Six-year projected probability of survival (OS) was 44% for Tx-1 and 63% for Tx-2 (P=0.3). The probability of attaining stringently defined complete remission (CR) or near complete remission (nCR) was 35% for Tx-1 and 48% for Tx-2; the sample size analyzed was not powered to detect a statistically significant difference between the two groups. Among patients randomized to Tx-1, attainment of CR or nCR was an essential prerequisite for extended OS (P=0.0001), EFS (P=0.000002) and TTP (P=0.000007). At the opposite, the benefits of double autologous transplantation were the greatest among patients who failed at least nCR. In particular, patients who did not attain CR or nCR after the first autologous transplantation and by study randomization received a second transplantation had a significantly longer duration of OS (P=0.01), EFS (P=0.000006) and TTP (P=0.000001) than patients who had the same response status but were assigned to receive a single autologous transplantation. Compared to Tx-1, Tx-2 significantly extended OS (P=0.04), EFS (P=0.000006) and TTP (P=0.000001) also among patients who failed Cr or nCR after receiving the entire treatment program to whom they were assigned (Tx-1 or Tx-2). At the opposite, for patients who were in CR or nCR after the first transplantation, there was no significant benefit from receiving a second autologous transplantation. In conclusion, data from the present analysis show that in comparison with a single autologous transplantation, i) double transplantation significantly prolonged EFS and TTP among younger (< 60 years) patients with previously untreated MM; ii) double autologous transplantation was of particular benefit for patients who failed at least nCR. Mature data derived from the final analysis of the study must be awaited before definite conclusions can be given concerning the impact of double autologous transplantation on the outcome of patients with MM. Supported by Università di Bologna, Progetti di Ricerca ex-60% (M.Cavo); Ministero dell’Università e Ricerca Scientifica, progetto FIRB, RBAU012E9A_001 (M. Cavo); and Fondazione Carisbo.

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A Phase II Study of Bortezomib (Velcade ®), Cyclophosphamide (Cytoxan®), Thalidomide (Thalomid®) and Dexamethasone as First-Line Therapy for Multiple Myeloma

Blood ◽

10.1182/blood.v112.11.94.94 ◽

2008 ◽

Vol 112 (11) ◽

pp. 94-94 ◽

Cited By ~ 6

Author(s):

William Bensinger ◽

Sundar Jagannath ◽

Robert Vescio ◽

Elber S. Camacho ◽

Jeffrey Lee Wolf ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Phase Ii ◽

Induction Therapy ◽

Response Rate ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Cell Harvest

Abstract Background: This phase II trial evaluated the response rate of sequential bortezomib (VELCADE®), cyclophosphamide (Cytoxan®), and dexamethasone ([VCD]; 3 cycles) followed by bortezomib, thalidomide (Thalomid®), and dexamethasone ([VTD]; 3 cycles) as first-line therapy for patients with multiple myeloma. The primary endpoints were overall response, achievement of „d very good partial response (VGPR), as well as assessment of safety and tolerability. Methods: Patients with newly diagnosed, untreated symptomatic myeloma were eligible. Treatment consisted of three 21-day cycles of bortezomib 1.3mg/m2 days 1, 4, 8, and 11, cyclophosphamide 300mg/m2 IV days 1 and 8 and dexamethasone 40mg p.o. or IV days 1, 2, 4, 5, 8, 9, 11, 12; followed by three 21-day cycles of bortezomib 1.0mg/m2 days 1, 4, 8, and 11; thalidomide 100 mg p.o. daily and dexamethasone same as cycles 1–3. Patients received thrombosis prophylaxis with ASA 325mg daily during cycles 4–6. Upon completion of the 6 cycles, patients proceeded to autologous stem cell harvest, transplant and/or maintenance therapy. Responses were defined as a decrease in serum and/or urine monoclonal (M) protein by 50% or greater. VGPR and other responses were as per the International Response Criteria. Results: This report provides results for all 44 eligible patients: median age 59 years; 68% male; 61% Stage III (D/S); documented ISS Stage II/III 59%; IgG 66%, IgA 17%; 17% light chain only. To date the first 30 patients are fully evaluable for response with 28-day post therapy follow up. The overall response rate (ORR; ≥PR) is 90% with 18/30 (60%) achieving CR + VGPR (CR 33%); 9/30 (30%) PR and 3/30 (10%) stable disease or not evaluable. Overall, both components of the sequential regimen were very well tolerated. One patient had a ruptured colonic diverticulum possibly related to dexamethasone, but recovered well and achieved VGPR on trial. There have been 49 therapy attributed toxicity events which have required drug/schedule adjustments. Of these, 9 events were Gd 3/4: 3 attributed to cyclophosphamide, 3 to dexamethasone, 2 attributed to bortezomib and 1 to thalidomide. DVT occurred in one patient who was at high risk because of prior bilateral hip surgery. Fourteen patients have proceeded to successful stem cell harvest and autologous transplant. Post transplant follow up as well as response information for all 44 patients will be presented. Conclusion: This bortezomib/cyclophosphamide/dexamethasone (VCD) based combination induction therapy followed by VTD is a promising addition to the treatment armamentarium for previously untreated patients. The response rates: ORR 90%; □ VGPR (60%) and CR (33%) are extremely encouraging and improve over our bortezomib/dexamethasone 2-drug experience which produced 90% □ PR and 38% □ VGPR. This very well tolerated new regimen is potentially an important step forward in induction therapy with presentation of more mature data. Supported by the Aptium Oncology Research Network and a research grant from Millennium Pharmaceuticals, Inc.

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The Clinical Impact of Macrofocal Disease in Multiple Myeloma Differs Between Presentation and Relapse

Blood ◽

10.1182/blood.v128.22.4431.4431 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4431-4431 ◽

Cited By ~ 2

Author(s):

Leo Rasche ◽

Amy Buros ◽

Niels Weinhold ◽

Caleb K. Stein ◽

James E McDonald ◽

...

Keyword(s):

Gene Expression ◽

Multiple Myeloma ◽

Research Funding ◽

Low Risk ◽

Disease Stage ◽

First Line ◽

Focal Lesions ◽

First Line Therapy ◽

Line Therapy

Abstract Introduction Functional imaging of Multiple Myeloma (MM) is redefining our knowledge of disease patterns. A pattern, termed macrofocal MM (macro MM), is defined by the presence of focal lesions and the absence of significant intervening bone marrow (BM) infiltration. At presentation, macro MM constitutes a distinct disease entity likely being associated with a favorable prognosis, although current evidence to support this is limited. Following first-line therapy, macrofocal patterns of disease emerge also in patients that initially presented with classical MM. In these patients the systemic BM involvement disappears in follow up examinations during treatment whereas focal lesions persist. In a third scenario, macrofocal patterns occur at overt relapse representing a patchy type of MM progression (Figure 1). The prognostic impact of a macrofocal pattern at these various disease stages is largely unknown. Therefore, we analyzed the clinical outcome and biological features of macro MM at different treatment stages. Patients and Methods 279 patients met the criteria of macro MM. Of those, 56 were at initial presentation, 48 at restaging following first line therapy, and 175 at relapse. Generally, macrofocal lesions were present in both positron emission tomography and magnetic resonance imaging. All first-line patients were treated with multi-agent induction therapy, autologous stem cell transplantation and received maintenance within prospective trials. Outcome results were compared to a set of cases with classical MM matched for age, gene-expression based (GEP) risk group, and treatment protocol. Results Macro MM at presentation is rare, constituting 6% of patients in the time period examined. The vast majority showed GEP-based low risk (94%). Age, Ig-type, and sex were not significantly different between macro MM and classical MM. With a median follow up of 8.6 years, only 10 of the macro MM patients relapsed. Compared to a matched-pair MM group, progression-free survival (PFS) and overall survival (OS) were significantly better in the macro MM group (P= 0.01 and 0.04 for PFS and OS, respectively). Thus macro MM at presentation constitutes a low risk form of MM. Focusing on the 10 macro MM cases who relapsed, no specific risk profile could be identified except >26 focal lesions on MRI was associated with a shorter PFS (P=0.04) but not with OS. Of note, although focal lesions frequently responded slowly, the time to response was not associated with outcome. To elucidate whether there are biological differences between MM cells in focal lesions and at differentially involved BM sites, we analyzed a set of 16 patients with paired samples from macrofocal lesions and iliac crest BM aspirates. No difference in a GEP based proliferation index was seen between the two sites. After correction for multiple testing we did not observe gene expression differences between them. A candidate gene study including a set of 27, myeloma relevant, adhesion molecules also did not reveal expression differences. In contrast to the situation at presentation, macrofocal patterns at restaging during initial therapy showed a 70% cumulative 24 months relapse incidence. The outcome of these cases was significantly worse in comparison to matched controls (P=0.02 and 0.02 for PFS and OS, respectively). Of note, all patients with macro MM showed an objective response at the time of imaging with 9 of 46 cases meeting the IMWG criteria for CR. Performing a similar analysis of patients with macro MM at relapse showed that 25% of patients presented with that pattern; a surprisingly high proportion. Extramedullary involvement was common (41%). Of note, 36% of patients repeatedly showed macrofocal patterns at subsequent relapses. PFS and OS at 2 years from macrofocal relapse were 24% and 39%, respectively. A matched group OS comparison was not possible since number of relapses and treatments were too different among the patients. Conclusions Macro MM at presentation seems to be an early stage of MM with an excellent prognosis. In contrast, a macrofocal pattern at restaging is associated with poor prognosis and early relapse. At this disease stage residual focal lesions may represent drug resistant clones. At overt relapse a macrofocal pattern was frequently seen, highlighting the need to integrate advanced imaging tools into the standard work up and indicating an important confounder of standard minimal residual disease diagnostics in MM. Disclosures Barlogie: Signal Genetics: Patents & Royalties. Davies:Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Morgan:Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Bristol Meyers: Consultancy, Honoraria; Janssen: Research Funding; Univ of AR for Medical Sciences: Employment.

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GCT-28. RECURRENCE PATTERN AND SURVIVAL FOR RELAPSED INTRACRANIAL NON-GERMINOMATOUS GERM CELL TUMORS: A SINGLE-INSTITUTION EXPERIENCE

Neuro-Oncology ◽

10.1093/neuonc/noaa222.248 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii333-iii333

Author(s):

Lei Wen ◽

Zhaoming Zhou ◽

Qingjun Hu ◽

Juan Li ◽

Mingyao Lai ◽

...

Keyword(s):

Germ Cell ◽

Germ Cell Tumors ◽

Late Recurrence ◽

Salvage Chemotherapy ◽

Recurrence Time ◽

First Line ◽

Primary Tumor Site ◽

First Line Therapy ◽

Line Therapy

Abstract PURPOSE Intracranial non-germinomatous germ cell tumors (NGGCTs) have lower overall survival than germinoma because relatively higher recurrence usually occurs after first line therapy. METHODS Between January 2003 and December 2018, 111 consecutive patients diagnosed with NGGCTs reviewed. Those who progressed after first line therapy were included in this study. Data of first line treatment, salvage treatment, clinicopathological features and survival were collected and analyzed. RESULTS Totally, thirty patients (30/111, 27.0%) relapsed in our cohort, including 19 patients with accurate relapse information detail, and 11 patients who died of disease progression during follow up but without exact time and site of relapse. The median OS from diagnosis of the disease was 49.2 months (95% CI: 14.1 to 84.3 months) and 3-year OS was 54.3%. Patients who received both CSI and chemotherapy relapsed less than those who received reduced volume of radiotherapy or only CSI or only chemotherapy (22.5% vs. 45.5%, p=0.034). Of 19 patients who had detail information of recurrence time and site, the median time from diagnosis of disease to relapse was 9.5 months (2.2 to 72.1 months). Regarding to recurrence site, most patients relapsed in primary site (10/19, 52.6%) or distant intracranial (6/19, 31.6%). The recurrence site of other 3 patients were spinal (n=1), ventricular (n=1) and peritoneal (n=1). CONCLUSION Protracted follow-up is recommended because late recurrence is not uncommon. Primary tumor site and distant intracranial are the most prevalent relapsed location. Patients who relapsed could benefited from both CSI and salvage chemotherapy.

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Bortezomib in first-line therapy is associated with falls in older adults with multiple myeloma

Journal of Geriatric Oncology ◽

10.1016/j.jgo.2021.02.009 ◽

2021 ◽

Author(s):

Kelly L. Schoenbeck ◽

Mark A. Fiala ◽

Tanya M. Wildes

Keyword(s):

Older Adults ◽

Multiple Myeloma ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Falls In Older Adults

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A Female with Evans Syndrome Presented with Pancytopenia

Journal of Enam Medical College ◽

10.3329/jemc.v10i2.53537 ◽

2021 ◽

Vol 10 (2) ◽

pp. 114-117

Author(s):

Md Rezaul Karim Chowdhury ◽

Md Haroon Ur Rashid ◽

Md Mahbub Hossain ◽

Shafayet Hossain Riyan

Keyword(s):

Oral Prednisolone ◽

Low Grade ◽

Evans Syndrome ◽

First Line ◽

Indirect Bilirubin ◽

First Line Therapy ◽

Line Therapy ◽

Immune Neutropenia ◽

Chronic Course

Evans syndrome is an uncommon haematological disorder characterised by autoimmune haemolytic anaemia (AIHA), immune thrombocytopenia (ITP) and/or immune neutropenia. It may occur in all ethnic groups, all ages and has no sex predilection. The direct antiglobulin test (DAT) is almost invariably positive. This condition generally runs a chronic course and is characterised by frequent exacerbations and remissions. Corticosteroids and/or intravenous immunoglobulin (IVIG) are the most commonly used first line therapy. Here we report a case of a female who presented with severe shortness of breath, palpitation and low grade fever and on examination she was found severely pale and mildly icteric. Her CBC and PBF showed pancytopenia. Indirect bilirubin and LDH were raised and direct Coomb’s test was positive. She was labeled as a case of Evans syndrome and responded to oral prednisolone. On subsequent follow-up her haematological profiles remained normal. J Enam Med Col 2020; 10(2): 114-117

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Analysis of Falls in Older Adults with Multiple Myeloma Undergoing First-Line Therapy

Blood ◽

10.1182/blood-2019-129611 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5886-5886

Author(s):

Kelly L. Schoenbeck ◽

Tanya M. Wildes ◽

Mark A. Fiala

Keyword(s):

Older Adults ◽

Multiple Myeloma ◽

Peripheral Neuropathy ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Increased Risk ◽

Risk Of Falls ◽

Falls In Older Adults ◽

First Line Treatment

Background: Patients with multiple myeloma are frequently treated with bortezomib, a proteasome inhibitor, which is associated with treatment-related peripheral neuropathy. Older adults are at increased risk of falls compared to the general population, often leading to associated morbidity and mortality. While an association between peripheral neuropathy and falls in older adults is well-established, the relationship between bortezomib and falls in older multiple myeloma patients is unknown. Our primary aim was to determine if older patients with multiple myeloma treated with bortezomib as first-line therapy had an increased incidence of falls within the first 12 months after starting treatment. Our secondary aim was to assess the overall survival of patients who fell compared to those who did not among patients who lived more than 12 months after initiating treatment. Methods: We analyzed the SEER-Medicare database for all patients 65 years old or older diagnosed with multiple myeloma between 2007 and 2013 and were enrolled in fee-for-service Medicare part A, B and D plans. The patients' corresponding Medicare claims data were analyzed through 2014 for myeloma treatments, fall claims, and covariates of interest. The primary outcome was accidental falls (E880-E888) occurring between 14 days to 12 months after starting multiple myeloma treatment. First-line therapy was defined as any anti-myeloma treatment administered within 14 days of starting multiple myeloma treatment, with bortezomib treatment being the focal independent variable. Cox regression was performed to determine the relative risk of having a fall after controlling for other covariates. Patients who started bortezomib after first-line therapy were censored at time of bortezomib commencement. The survival analysis included only patients who survived more than 12 months of starting treatment to allow landmark analysis of falls in the first year. Results: Of 4,084 older adults with new multiple myeloma diagnoses undergoing first-line therapy, the median age was 75 (range 65-97) with 51% males. Bortezomib was used in first-line therapy for 2,052 (50%) patients, of which 157 (8%) patients experienced a fall within 12 months after starting treatment compared to 102 (5%) of patients not receiving bortezomib (p < 0.001). Bortezomib was associated with a 28% increase risk of falls (HR 1.29; 95% CI 1.00-1.65; p = 0.047). In multivariate analysis, bortezomib was not associated with an increased incidence of falls after controlling for age, gender, race, proxies for Charlson Comorbidity Index (CCI) and poor performance status, pre-existing peripheral neuropathy, falls within the 12 months prior to starting first-line myeloma treatment, depression, polypharmacy, and first-line treatment with lenalidomide (Table 1). Advancing age, history of fall(s), depression, and polypharmacy (defined as more than 10 unique prescription medications at initiation of first-line treatment), were all associated with an increased risk of falls, consistent with prior literature. In a landmark analysis of those who survived 12 months following the start of treatment, a fall was associated with a 26% increased risk of hazard for death (aHR 1.26; 95% CI 1.02-1.56; p = 0.033) after controlling for other covariates. The median OS of those with a fall was 35.7 months (95% CI 29.1-48.4) compared to 49.1 months (95% CI 47.1-52.8) for those without (p < 0.0001). Conclusion: In older adults with multiple myeloma, treatment with bortezomib was not associated with increased risk of a patient having a diagnostic code for falls. However, experiencing a fall within the year after starting treatment was associated with decreased overall survival. Limitations of the study include that the incidence of falls is likely underestimated in billing data, given prior data from our group showing a rate of self-reported falls of 26% in the year after diagnosis. Additional research, including prospective trials involving fall assessments, should be considered in older patients with multiple myeloma. Disclosures Wildes: Janssen: Research Funding; Carevive: Consultancy. Fiala:Incyte: Research Funding.

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