Characteristics of Multiple Myeloma Patients with Multiple Lines of Therapy Using Real-World US Claims Data

Abstract Background: Multiple myeloma is an incurable disease with poor survival rate. Recently, novel treatments have focused on addressing unmet needs among heavily pre-treated patients who have failed prior therapies. The purpose of this analysis was to describe the characteristics of patients who are heavily pre-treated vs patients who were not, within 2 years of initiating MM therapy. Results of this analysis will help to understand the characteristics, including treatment patterns and burden, of MM patients who progress through lines of therapy over a relatively short time period. Methods: Using a US administrative claims database (Truven Health MarketScan® Database), adult patients (age ≥18) were included in the analysis if they had 1) ≥2 MM diagnoses codes (ICD-9 203.0x) on different dates between Jan 1, 2005-Mar 31, 2014 (study period); 2) MM treatment between Jan 1, 2007-Mar 31, 2012 and within 90 days of an MM diagnosis code (date of the first MM treatment set as the index date); and 3) continuous eligibility for medical insurance 24 months pre/postindex. Patients were excluded if they had 1) MM treatment during 24 months preindex; or during 24 month pre/post index had 2) moved from commercial insurance to Medicare; 3) non-MM chemotherapy; 4) pregnancy-related or stem cell transplant codes; or 5) HIV diagnosis during study period. An algorithm using dispensing dates and days supply was developed to define line of therapy (LOT) and double refractory. A new LOT was identified where there was a ≥60 day gap with no treatment, a ≥60 day gap followed by retreatment with the same drug, or where there was a change in therapy based on 30 day windows and the summed days supply of medication was >60 days. Refractory events were defined when a PI or IMiD had days supply for <60 days, was discontinued for ≥60 days, a different PI or IMiD was initiated and the initial drug did not appear in the next LOT. Heavily pre-treated was defined as starting an LOT after having received ≥3 prior LOT that included a PI and IMiD or double refractory to both PI and IMiD. Chi-square test was used to test for differences in categorical variables and Mann Whitney U test for continuous variables. Results: A total of 1109 patients were included in the analysis. The percent of patients with 1, 2, 3, 4 or >4 LOT were 39.8%, 33.0%, 15.4% and 6.1% and 5.7%, respectively. A single refractory event occurred in 66 (6.0%) patients and 2 (0.2%) patients were identified as double refractory. There were 80 (7.2%) patients who were heavily pre-treated. The heavily pre-treated group had a similar percent of males (56.3%) as the non-heavily pre-treated group (54.9%; p=0.82). The heavily pre-treated group was slightly younger (66.1 vs 70.9 years; p=0.0008) and had a lower percent with Medicare coverage (55.0% vs 71.1%; p=0.0024). The heavily pre-treated group had a substantially higher percent of regimens that included both PI and IMiD in the 1st LOT (28.8% vs 7.4%; p<0.0001). The most common 1st LOT drug regimens for the heavily pre-treated group were bortezomib (BOR) (21.31%), thalidomide (THAL) (21.3%), lenalidomide/bortezomib (LEN/BOR) (20.0%), and lenalidomide (LEN) (18.8%). In the non-heavily pre-treated group the most common 1st LOT regimens were LEN (36.7%), BOR (20.4%), THAL (14.4%), and melphalan (10.1%). Patients who were heavily pre-treated reached their 2nd LOT in fewer days than non-heavily pre-treated (152.5 vs 279.9 days; p<0.0001). There was a much higher percent of patients using BOR/LEN in the 2nd LOT in the heavily pre-treated than non-heavily pre-treated (20.0% vs. 4.1%). Conclusions: In this analysis, 7.2% of non-stem cell transplant patients were heavily pre-treated at 2 years after initiating MM therapy. Heavily pre-treated patients had a faster time to initiation of 2nd LOT. They also tended to be younger. Moreover, heavily pre-treated patients were more likely to have had both a PI and IMiD as their initial therapy. Patients who were heavily pre-treated in this analysis may have had faster disease progression, which may have led to becoming heavily pre-treated within the follow-up time of the study. Additional research should further explore the disease and economic burden of these patients. Disclosures Maiese: Janssen Scientific Affairs, LLC: Employment. Macomson:Janssen Scientific Affairs, LLC: Employment. Kozma:Janssen Scientific Affairs, LLC: Consultancy. Slaton:Janssen Scientific Affairs, LLC: Consultancy. Senbetta:Janssen Scientific Affairs, LLC: Employment.

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Autologous Stem Cell Transplant in Patients with Multiple Myeloma Previously Treated with Lenalidomide: A Single-Institution Experience Using An Intermediate-Dose Cyclophosphamide-Based Regimen

Blood ◽

10.1182/blood.v118.21.4391.4391 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4391-4391

Author(s):

Asif Alavi ◽

Rada Grubovic ◽

Gary J. Schiller

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplant ◽

Treated Group ◽

Median Number ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

Cd34 Cells ◽

Peripheral Stem Cells

Abstract Abstract 4391 Background: High dose chemotherapy followed by autologous transplantation of peripheral blood stem cells plays an important role in the management of intermediate- and advanced-stage multiple myeloma. In order for successful engraftment to occur, adequate numbers of high quality peripheral stem cells must be harvested prior to transplantation. Mobilization of PBSC in patients treated with lenalidomide has been associated with poor apheresis collections after G-CSF mobilization. The purpose of this study is to present our institution’s experience utilizing an intermediate-dose cyclophosphamide-based mobilization regimen. Methods: We retrospectively analyzed data for patients with multiple myeloma who underwent autologous stem cell transplant at UCLA between 2006 and 2010. Data were obtained from the database of the UCLA Heme Malignancy/Stem Cell Transplant Unit, the electronic health record system and stem cell processing laboratory. All patients underwent mobilization with a regimen of cyclophosphamide 2.5g/m2 IVPB, G-CSF 10 mcg/kg/day for 4 days SQ, and prednisone 2mg/kg/day for 4 days po. The number of CD 34+ cells was used as a marker for the number of peripheral stem cells collected. Minimum dose collected to ensure adequate engraftment was 2×106/kg CD34+ cells. Patients were conditioned with melphalan 100mg/m2/d x2 (unless there was evidence of renal failure, in which case the dose was reduced to 100mg/m2) with subsequent infusion of stem cells. Neutrophil engraftment was defined as the first day of absolute neutrophil count greater than 500×106/L ≥ 7 days after transplant. Results: Autologous stem cell transplant was performed in 103 patients with multiple myeloma at UCLA between 2006 and 2010. Median number of apheresis procedures was 1 (1–12) with a median of 4.4×106/kg (1.4–33.5) CD34+ cells collected. Median time to engraftment was 10 (8–18) days. Thirty-five patients received lenalidomide at some point in their pretransplant treatment. Median number of apheresis procedures was 1 in both lenalidomide and non lenalidomide treated groups. In the lenalidomide treated group 54% required only one collection versus 75% in the non lenalidomide treated group (p=0.033). In the lenalidomide treated group 31% required 3 more or more collections versus 10% in non lenalidomide treated group (p=0.0075). Three patients in the lenalidomide group had subsequent mobilization with plerixafor with one of these requiring bone marrow harvesting. Median CD34+ cells collected was 3.5×106/kg and 4.9×106/kg (p=0.246) in the lenalidomide and non-lenalidomide groups respectively. Both groups had a median time to neutrophil engraftment of 10 days with a similar range. Conclusion: Pre-transplant use of lenalidomide adversely affected the number of stem cell apheresis procedures required to procure adequate stem cell dose as evidenced by a greater percentage requiring 3 or more collections. However, despite prior lenalidomide exposure, the use of our mobilization regimen permitted adequate collection, with the majority of patients requiring only one apheresis procedure, and led to an equivalent time to neutrophil recovery. Disclosures: Off Label Use: Cyclophosphamide and G-CSF for mobilization of stem cells.

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Pericardial relapse of multiple myeloma

BMJ Case Reports ◽

10.1136/bcr-2019-233340 ◽

2020 ◽

Vol 13 (4) ◽

pp. e233340

Author(s):

Lee S Jamison ◽

Clifton Craig Mo ◽

Mary Kwok

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Poor Prognosis ◽

Stem Cell Transplant ◽

Complete Response ◽

Initial Therapy ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

Extramedullary Relapse ◽

To Receive

In patients who experience relapse of multiple myeloma, upwards of 30% can have extramedullary disease. The presence of extramedullary multiple myeloma is typically associated with adverse cytogenetics and a poor prognosis. Organs most commonly involved include the liver, skin, central nervous system, pleural effusions, kidney, lymph nodes, and pancreas. We present the case of a 53-year-old man with IgA kappa multiple myeloma with the adverse cytogenetic findings of t(4;14) and 1q21 gain who had achieved a stringent complete (sCR) response after initial therapy with carfilzomib, lenalidomide and dexamethasone. Stringent complete response is defined as the normalization of the free light chain ratio in the serum and an absence of clonal cells in the bone marrow in additiion to criteria needed to achieve complete response. Prior to undergoing a planned autologous stem cell transplant, this patient experienced cardiac tamponade secondary to extramedullary relapse of his multiple myeloma which was limited to the pericardium. In response, his treatment regimen was transitioned to pomalidomide, bortezomib, dexamethasone and cyclophosphamide for three cycles after which he again achieved sCR and ultimately underwent autologous stem cell transplant. Post-transplant consolidation therapy was administered in the form of pomalidomide, bortezomib and dexamethasone, followed by pomalidomide and bortezomib maintenance, which he has continued to receive for 3 years without evidence of disease progression.

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255. Breakthrough Mucormycosis (BT-MCR) on Antifungals Having Mucorales Activity Portrays Worse Prognosis compared with BT-MCR on Mold-Active Antifungals with no Mucorales Activity

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.330 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S142-S142 ◽

Cited By ~ 2

Author(s):

Dierdre B Axell-House ◽

Ying Jiang ◽

Andreas Kyvernitakis ◽

Russel E Lewis ◽

Issam I Raad ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplant ◽

Cox Regression ◽

Hematologic Malignancies ◽

Categorical Variables ◽

Cancer Center ◽

Cell Transplant ◽

Continuous Variables ◽

Group A ◽

Group B

Abstract Background BT-MCR is known to develop in the setting of agents having Aspergillus but no Mucorales activity. However, BT-MCR can occur even with the use of antifungals having with Mucorales activity in patients with hematologic malignancies and or stem cell transplant (HM). Methods We reviewed the records of HM patients treated for MCR (1994 to 2019) at MD Anderson Cancer Center. We identified patients with BT-MCR on antifungals having Mucorales activity: posaconazole (POSA), isavuconazole (ISA), and amphotericin B (AMB) (group A), and patients with BT-MCR on agents having Aspergillus but no Mucorales activity: voriconazole (VRC), itraconazole (ITZ), echinocandins (group B). BT-MCR was defined as MCR diagnosis (dx) after ≥7days (d) of antifungal use. The primary outcome was 42d mortality after the BT-MCR dx. Chi-square or Fisher’s exact test was used for categorical variables and Wilcoxon rank-sum test used for continuous variables. Cox regression model was used to evaluate the independent variables on outcome. Results We identified 11 patients in group A (3 POSA, 5 ISA, 3 AMB) and 81 patients in group B (61 VRC, 13 echinocandins, 7 ITZ). Both groups were not different in terms of age, sex, underlying HM (AML/MDS in 100% vs. 88% in groups A and B, respectively), status of HM (active disease in 82% vs. 67%), prior stem cell transplant (45% vs. 54%) or GvHD (80% vs. 84%), neutropenia at dx (55% vs. 42%), prior receipt of >600 mg of prednisone (45% vs. 41%) or ICU at MCR dx (36% vs. 26%). Similarly, Mucorales species (Rhizopus spp. in 55% vs. 49%) and type of infection (sino-pulmonary in 73% vs. 68%) were no different between the groups. However, both d42 (82% vs. 46%, P = 0.025) and d84 (100% vs. 60%, P = 0.007) mortality was worse in group A. Similarly, median time to death was faster in patients in group A (26d, range 7-80d), vs. group B (42d, range 4–3146d, P = 0.031). Kaplan–Meier analysis showed a similar difference (Figure 1). In multivariate analysis, neutropenia (P = 0.038) and ICU at dx (P = 0.002) were independent factors on day 42d mortality in all 92 patients with prior Mucorales–active antifungals showing a trend associated with poor outcome (P = 0.17). Conclusion BT-MCR on agents having Mucorales activity is a marker of poor prognosis in HM patients. Early use of investigational immunotherapy and salvage antifungal chemotherapy studies is needed in that subgroup of patients. Disclosures All authors: No reported disclosures.

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Post-Autologous (ASCT) Stem Cell Transplant Therapy in Multiple Myeloma

Advances in Hematology ◽

10.1155/2014/652395 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 10

Author(s):

Zeina Al-Mansour ◽

Muthalagu Ramanathan

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

High Risk ◽

Stem Cell Transplant ◽

Maintenance Phase ◽

Progression Free Survival ◽

Initial Therapy ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

Meaningful Improvement

Autologous stem cell transplant (ASCT) is the standard of care in transplant-eligible multiple myeloma patients and is associated with significant improvement in progression-free survival (PFS), complete remission rates (CR), and overall survival (OS). However, majority of patients eventually relapse, with a median PFS of around 36 months. Relapses are harder to treat and prognosis declines with each relapse. Achieving and maintaining “best response” to initial therapy is the ultimate goal of first-line treatment and sustained CR is a powerful surrogate for extended survival especially in high-risk multiple myeloma. ASCT is often followed by consolidation/maintenance phase to deepen and/or maintain the response achieved by induction and ASCT. Novel agents like thalidomide, lenalidomide, and bortezomib have been used as single agents or in combination. Thalidomide use has been associated with a meaningful improvement in PFS and EFS, however, with substantial side effects. Data with lenalidomide maintenance after-ASCT is favorable, but the optimal duration of lenalidomide maintenance is still unclear. Bortezomib use has been associated with superior outcomes, predominantly in high-risk myeloma patients. Combination regimens utilizing a proteasome inhibitor (i.e., bortezomib) with an immunomodulatory drug (thalidomide or lenalidomide) have provided the best outcomes. This review article serves as a review of the best available evidence in post-ASCT approaches in multiple myeloma.

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