Sarvari Yellapragada, MD

Background

Lenalidomide, bortezomib, and dexamethasone (RVD) is standard triplet induction for fit newly-diagnosed myeloma (NDMM) patients, with response rate (RR)>90%. A 21-day cycle with bortezomib given days 1, 4, 8, and 11 (2x/w) is standard. However, up to 80% of patients develop neuropathy. Weekly bortezomib dosing (1x/w), subcutaneous route, and 28- to 35-day cycle length may optimize tolerance. We present an effectiveness and toxicity analysis of Veterans who received RVD with 1x/w and 2x/w bortezomib for NDMM.

Methods

The VA Corporate Data Warehouse identified 1499 Veterans with NDMM given RVD ≤42 days of treatment start. 840 Veterans were grouped for initial analysis based on criteria: 1) lenalidomide and ≥ 3 bortezomib doses during cycle 1; 2) ≥6 mean days between bortezomib treatments=1x/w); and 3) number of lenalidomide days informed cycle length (21d, 28d, or 35d; default 7-day rest). Investigators reviewed algorithm results to finalize group assignments. Endpoints included depth of response, time to next treatment (TTNT), overall survival (OS), and neuropathy. Neuropathy was defined as use of neuropathy medications and neuropathy ICD-10 codes.

Results

Our algorithm correctly assigned 82% of 840 cycle 1 RVD schedules. The largest groups were 21d 1x/w (n=291), 21d 2x/w (n=193), 28d 1x/w (n=188), and 28d 2x/w (n=82). Median age was 68.3; 53% were non-Hispanic White. Demographics and ISS stage of groups were similar. 30% underwent autologous transplant. Tolerability. Median number of bortezomib doses ranged from 22.5-25.5 (p=0.57). Neuropathy favored 1x/w, 17.7 vs 30.2% (p=0.0001) and was highest (34.7%) in 21d 2x/w. Effectiveness. Response was assessable for 28% of patients. RR (72%, p=0.68) and median TTNT (19.3 months, p=0.20) were similar, including 1x/w vs 2x/w comparison (p=0.79). 21d regimens optimized TTNT (21.4 vs 13.9 months, p=0.045) and trended to better OS (73 vs 65 months, p=0.06).

Conclusions

1x/w RVD preserved effectiveness compared to “standard” RVD in a large Veteran cohort. 1x/w reduced neuropathy incidence. 28d regimens demonstrated inferior longer-term outcomes. Certain endpoints, such as RR and neuropathy, appear underestimated due to data source limitations. 21d 1x/w RVD optimizes effectiveness, tolerability, and administration and should be considered for broader utilization in Veterans with NDMM.

Background

Lenalidomide, bortezomib, and dexamethasone (RVD) is standard triplet induction for fit newly-diagnosed myeloma (NDMM) patients, with response rate (RR)>90%. A 21-day cycle with bortezomib given days 1, 4, 8, and 11 (2x/w) is standard. However, up to 80% of patients develop neuropathy. Weekly bortezomib dosing (1x/w), subcutaneous route, and 28- to 35-day cycle length may optimize tolerance. We present an effectiveness and toxicity analysis of Veterans who received RVD with 1x/w and 2x/w bortezomib for NDMM.

Methods

The VA Corporate Data Warehouse identified 1499 Veterans with NDMM given RVD ≤42 days of treatment start. 840 Veterans were grouped for initial analysis based on criteria: 1) lenalidomide and ≥ 3 bortezomib doses during cycle 1; 2) ≥6 mean days between bortezomib treatments=1x/w); and 3) number of lenalidomide days informed cycle length (21d, 28d, or 35d; default 7-day rest). Investigators reviewed algorithm results to finalize group assignments. Endpoints included depth of response, time to next treatment (TTNT), overall survival (OS), and neuropathy. Neuropathy was defined as use of neuropathy medications and neuropathy ICD-10 codes.

Results

Our algorithm correctly assigned 82% of 840 cycle 1 RVD schedules. The largest groups were 21d 1x/w (n=291), 21d 2x/w (n=193), 28d 1x/w (n=188), and 28d 2x/w (n=82). Median age was 68.3; 53% were non-Hispanic White. Demographics and ISS stage of groups were similar. 30% underwent autologous transplant. Tolerability. Median number of bortezomib doses ranged from 22.5-25.5 (p=0.57). Neuropathy favored 1x/w, 17.7 vs 30.2% (p=0.0001) and was highest (34.7%) in 21d 2x/w. Effectiveness. Response was assessable for 28% of patients. RR (72%, p=0.68) and median TTNT (19.3 months, p=0.20) were similar, including 1x/w vs 2x/w comparison (p=0.79). 21d regimens optimized TTNT (21.4 vs 13.9 months, p=0.045) and trended to better OS (73 vs 65 months, p=0.06).

Conclusions

1x/w RVD preserved effectiveness compared to “standard” RVD in a large Veteran cohort. 1x/w reduced neuropathy incidence. 28d regimens demonstrated inferior longer-term outcomes. Certain endpoints, such as RR and neuropathy, appear underestimated due to data source limitations. 21d 1x/w RVD optimizes effectiveness, tolerability, and administration and should be considered for broader utilization in Veterans with NDMM.

Background

Lenalidomide, bortezomib, and dexamethasone (RVD) is standard triplet induction for fit newly-diagnosed myeloma (NDMM) patients, with response rate (RR)>90%. A 21-day cycle with bortezomib given days 1, 4, 8, and 11 (2x/w) is standard. However, up to 80% of patients develop neuropathy. Weekly bortezomib dosing (1x/w), subcutaneous route, and 28- to 35-day cycle length may optimize tolerance. We present an effectiveness and toxicity analysis of Veterans who received RVD with 1x/w and 2x/w bortezomib for NDMM.

Methods

The VA Corporate Data Warehouse identified 1499 Veterans with NDMM given RVD ≤42 days of treatment start. 840 Veterans were grouped for initial analysis based on criteria: 1) lenalidomide and ≥ 3 bortezomib doses during cycle 1; 2) ≥6 mean days between bortezomib treatments=1x/w); and 3) number of lenalidomide days informed cycle length (21d, 28d, or 35d; default 7-day rest). Investigators reviewed algorithm results to finalize group assignments. Endpoints included depth of response, time to next treatment (TTNT), overall survival (OS), and neuropathy. Neuropathy was defined as use of neuropathy medications and neuropathy ICD-10 codes.

Results

Our algorithm correctly assigned 82% of 840 cycle 1 RVD schedules. The largest groups were 21d 1x/w (n=291), 21d 2x/w (n=193), 28d 1x/w (n=188), and 28d 2x/w (n=82). Median age was 68.3; 53% were non-Hispanic White. Demographics and ISS stage of groups were similar. 30% underwent autologous transplant. Tolerability. Median number of bortezomib doses ranged from 22.5-25.5 (p=0.57). Neuropathy favored 1x/w, 17.7 vs 30.2% (p=0.0001) and was highest (34.7%) in 21d 2x/w. Effectiveness. Response was assessable for 28% of patients. RR (72%, p=0.68) and median TTNT (19.3 months, p=0.20) were similar, including 1x/w vs 2x/w comparison (p=0.79). 21d regimens optimized TTNT (21.4 vs 13.9 months, p=0.045) and trended to better OS (73 vs 65 months, p=0.06).

Conclusions

1x/w RVD preserved effectiveness compared to “standard” RVD in a large Veteran cohort. 1x/w reduced neuropathy incidence. 28d regimens demonstrated inferior longer-term outcomes. Certain endpoints, such as RR and neuropathy, appear underestimated due to data source limitations. 21d 1x/w RVD optimizes effectiveness, tolerability, and administration and should be considered for broader utilization in Veterans with NDMM.

Background

In 3/2021, chimeric antigen receptor (CAR) T-cell therapy was approved for the treatment of multiple myeloma in adult patients with refractory disease. Currently, only the Veterans Affair (VA) center at the Tennessee Valley Healthcare System (TVHS) offers this treatment. Herein, we report a significant healthcare milestone in 2024 when the first patient received CAR T-cell therapy for multiple myeloma in the VA system. Additionally, the rate of hypogammaglobulinemia is the highest for CAR T-cell therapy using idecabtagene vicleucel compared to therapies using other antineoplastic agents (Wat et al, 2021). The complications of hypogammaglobulinemia can be mitigated by intravenous immunoglobulin (IVIG) treatment.

Case Presentation

A 75-year-old male veteran was diagnosed with IgA Kappa multiple myeloma and received induction therapy with bortezomib, lenalidomide, and dexamethasone in 2014. The patient underwent autologous stem cell transplant (SCT) in the same year. His disease recurred in 3/2019, and the patient was started on daratumumab and pomalidomide. He received another autologous SCT in 2/2021, to which he was refractory. The veteran then received treatment with daratumumab and ixazomib, followed by carfilzomib and cyclophosphamide. Starting in 9/2022, the patient also required regular IVIG treatment for hypogammaglobulinemia. He eventually received CAR T-cell therapy with idecabtagene vicleucel at THVS on 4/18/2024. The patient tolerated the treatment well and is undergoing routine disease monitoring. Following CAR T-cell therapy, his hypogammaglobulinemia persists with immunoglobulins level less than 500 mg/dL, and the veteran is still receiving supportive care IVIG.

Discussion

A population estimate of 1.3 million veterans are uninsured and can only access healthcare through the VA (Nelson et al, 2007). This case highlights the first patient to receive CAR T-cell therapy for multiple myeloma in the VA system, indicating that veterans now have access to this life-saving treatment. The rate of hypogammaglobulinemia following CAR T-cell therapy for multiple myeloma is as high as 41%, with an associated infection risk of 70%. Following CAR T-cell therapy with idecabtagene vicleucel, around 61% of patients will require IVIG treatment (Wat el al, 2021). Our case adds to this growing literature on the prevalence of IVIG treatment following CAR T-cell therapy in this patient population.

Background

In 3/2021, chimeric antigen receptor (CAR) T-cell therapy was approved for the treatment of multiple myeloma in adult patients with refractory disease. Currently, only the Veterans Affair (VA) center at the Tennessee Valley Healthcare System (TVHS) offers this treatment. Herein, we report a significant healthcare milestone in 2024 when the first patient received CAR T-cell therapy for multiple myeloma in the VA system. Additionally, the rate of hypogammaglobulinemia is the highest for CAR T-cell therapy using idecabtagene vicleucel compared to therapies using other antineoplastic agents (Wat et al, 2021). The complications of hypogammaglobulinemia can be mitigated by intravenous immunoglobulin (IVIG) treatment.

Case Presentation

A 75-year-old male veteran was diagnosed with IgA Kappa multiple myeloma and received induction therapy with bortezomib, lenalidomide, and dexamethasone in 2014. The patient underwent autologous stem cell transplant (SCT) in the same year. His disease recurred in 3/2019, and the patient was started on daratumumab and pomalidomide. He received another autologous SCT in 2/2021, to which he was refractory. The veteran then received treatment with daratumumab and ixazomib, followed by carfilzomib and cyclophosphamide. Starting in 9/2022, the patient also required regular IVIG treatment for hypogammaglobulinemia. He eventually received CAR T-cell therapy with idecabtagene vicleucel at THVS on 4/18/2024. The patient tolerated the treatment well and is undergoing routine disease monitoring. Following CAR T-cell therapy, his hypogammaglobulinemia persists with immunoglobulins level less than 500 mg/dL, and the veteran is still receiving supportive care IVIG.

Discussion

A population estimate of 1.3 million veterans are uninsured and can only access healthcare through the VA (Nelson et al, 2007). This case highlights the first patient to receive CAR T-cell therapy for multiple myeloma in the VA system, indicating that veterans now have access to this life-saving treatment. The rate of hypogammaglobulinemia following CAR T-cell therapy for multiple myeloma is as high as 41%, with an associated infection risk of 70%. Following CAR T-cell therapy with idecabtagene vicleucel, around 61% of patients will require IVIG treatment (Wat el al, 2021). Our case adds to this growing literature on the prevalence of IVIG treatment following CAR T-cell therapy in this patient population.

Background

In 3/2021, chimeric antigen receptor (CAR) T-cell therapy was approved for the treatment of multiple myeloma in adult patients with refractory disease. Currently, only the Veterans Affair (VA) center at the Tennessee Valley Healthcare System (TVHS) offers this treatment. Herein, we report a significant healthcare milestone in 2024 when the first patient received CAR T-cell therapy for multiple myeloma in the VA system. Additionally, the rate of hypogammaglobulinemia is the highest for CAR T-cell therapy using idecabtagene vicleucel compared to therapies using other antineoplastic agents (Wat et al, 2021). The complications of hypogammaglobulinemia can be mitigated by intravenous immunoglobulin (IVIG) treatment.

Case Presentation

A 75-year-old male veteran was diagnosed with IgA Kappa multiple myeloma and received induction therapy with bortezomib, lenalidomide, and dexamethasone in 2014. The patient underwent autologous stem cell transplant (SCT) in the same year. His disease recurred in 3/2019, and the patient was started on daratumumab and pomalidomide. He received another autologous SCT in 2/2021, to which he was refractory. The veteran then received treatment with daratumumab and ixazomib, followed by carfilzomib and cyclophosphamide. Starting in 9/2022, the patient also required regular IVIG treatment for hypogammaglobulinemia. He eventually received CAR T-cell therapy with idecabtagene vicleucel at THVS on 4/18/2024. The patient tolerated the treatment well and is undergoing routine disease monitoring. Following CAR T-cell therapy, his hypogammaglobulinemia persists with immunoglobulins level less than 500 mg/dL, and the veteran is still receiving supportive care IVIG.

Discussion

A population estimate of 1.3 million veterans are uninsured and can only access healthcare through the VA (Nelson et al, 2007). This case highlights the first patient to receive CAR T-cell therapy for multiple myeloma in the VA system, indicating that veterans now have access to this life-saving treatment. The rate of hypogammaglobulinemia following CAR T-cell therapy for multiple myeloma is as high as 41%, with an associated infection risk of 70%. Following CAR T-cell therapy with idecabtagene vicleucel, around 61% of patients will require IVIG treatment (Wat el al, 2021). Our case adds to this growing literature on the prevalence of IVIG treatment following CAR T-cell therapy in this patient population.

Background

In 2024, the first two veterans, both from the Michael E. DeBakey Veteran Affairs (VA) Medical Center, received chimeric antigen receptors (CAR) T-cell therapy for refractory multiple myeloma through the Tennessee Valley Healthcare System (TVHS). Currently, TVHS is the only VA where this treatment is available. One of these patients also had penta-refractory multiple myeloma (P-RMM), which is associated with significantly worse progression-free survival and overall survival (OS) (Gill et al, 2021). P-RMM is defined as resistance to at least two immunomodulatory drugs, two different proteasome inhibitors, and one CD38 monoclonal antibody.

Case Presentation

A 71-year-old female veteran was diagnosed with high-risk multiple myeloma and received induction therapy with carfilzomib, lenalidomide, and dexamethasone in 2017. She underwent autologous stem cell transplant (SCT) in 4/2018. The veteran subsequently received maintenance therapy with lenalidomide, bortezomib, and dexamethasone. Her disease recurred in 1/2022. The patient then received two more lines of treatments with daratumumab and pomalidomide followed by selinexor. She had another autologous SCT in 5/2023, to which she was refractory. Her fifth line therapy included addition of bortezomib to her selinexor regimen. She eventually underwent CAR T-cell therapy at THVS on 5/1/2024 with good tolerance of therapy. At her follow-up visit, the patient had significant response to CAR T-cell treatment, based on her symptoms and improvement in free light chains and serum protein electrophoresis.

Discussion

CAR T-cell therapy is one of the newest and most cutting-edge therapies for patients with refractory multiple myeloma. Access to this therapy has been limited throughout the country. However, as shown by our case, this life-saving treatment is now available to patients within the VA. According to a retrospective study on P-RMM patients, the OS in patients who received B-cell maturation antigen (BCMA) targeted therapy was significantly higher than in those who did not (17 vs. 6 months, p < 0.0001). Among the BCMA-targeted therapies, CAR T-cell therapy is associated with the highest OS (29 months) compared to antibody-drug conjugates and bispecific T-cell engagers (Atrash et al, 2023). Thus, accessibility to CAR T-cell therapy was essential in our patient with P-RMM in ensuring her best survival outcomes.

Background

In 2024, the first two veterans, both from the Michael E. DeBakey Veteran Affairs (VA) Medical Center, received chimeric antigen receptors (CAR) T-cell therapy for refractory multiple myeloma through the Tennessee Valley Healthcare System (TVHS). Currently, TVHS is the only VA where this treatment is available. One of these patients also had penta-refractory multiple myeloma (P-RMM), which is associated with significantly worse progression-free survival and overall survival (OS) (Gill et al, 2021). P-RMM is defined as resistance to at least two immunomodulatory drugs, two different proteasome inhibitors, and one CD38 monoclonal antibody.

Case Presentation

A 71-year-old female veteran was diagnosed with high-risk multiple myeloma and received induction therapy with carfilzomib, lenalidomide, and dexamethasone in 2017. She underwent autologous stem cell transplant (SCT) in 4/2018. The veteran subsequently received maintenance therapy with lenalidomide, bortezomib, and dexamethasone. Her disease recurred in 1/2022. The patient then received two more lines of treatments with daratumumab and pomalidomide followed by selinexor. She had another autologous SCT in 5/2023, to which she was refractory. Her fifth line therapy included addition of bortezomib to her selinexor regimen. She eventually underwent CAR T-cell therapy at THVS on 5/1/2024 with good tolerance of therapy. At her follow-up visit, the patient had significant response to CAR T-cell treatment, based on her symptoms and improvement in free light chains and serum protein electrophoresis.

Discussion

CAR T-cell therapy is one of the newest and most cutting-edge therapies for patients with refractory multiple myeloma. Access to this therapy has been limited throughout the country. However, as shown by our case, this life-saving treatment is now available to patients within the VA. According to a retrospective study on P-RMM patients, the OS in patients who received B-cell maturation antigen (BCMA) targeted therapy was significantly higher than in those who did not (17 vs. 6 months, p < 0.0001). Among the BCMA-targeted therapies, CAR T-cell therapy is associated with the highest OS (29 months) compared to antibody-drug conjugates and bispecific T-cell engagers (Atrash et al, 2023). Thus, accessibility to CAR T-cell therapy was essential in our patient with P-RMM in ensuring her best survival outcomes.

Background

In 2024, the first two veterans, both from the Michael E. DeBakey Veteran Affairs (VA) Medical Center, received chimeric antigen receptors (CAR) T-cell therapy for refractory multiple myeloma through the Tennessee Valley Healthcare System (TVHS). Currently, TVHS is the only VA where this treatment is available. One of these patients also had penta-refractory multiple myeloma (P-RMM), which is associated with significantly worse progression-free survival and overall survival (OS) (Gill et al, 2021). P-RMM is defined as resistance to at least two immunomodulatory drugs, two different proteasome inhibitors, and one CD38 monoclonal antibody.

Case Presentation

A 71-year-old female veteran was diagnosed with high-risk multiple myeloma and received induction therapy with carfilzomib, lenalidomide, and dexamethasone in 2017. She underwent autologous stem cell transplant (SCT) in 4/2018. The veteran subsequently received maintenance therapy with lenalidomide, bortezomib, and dexamethasone. Her disease recurred in 1/2022. The patient then received two more lines of treatments with daratumumab and pomalidomide followed by selinexor. She had another autologous SCT in 5/2023, to which she was refractory. Her fifth line therapy included addition of bortezomib to her selinexor regimen. She eventually underwent CAR T-cell therapy at THVS on 5/1/2024 with good tolerance of therapy. At her follow-up visit, the patient had significant response to CAR T-cell treatment, based on her symptoms and improvement in free light chains and serum protein electrophoresis.

Discussion

CAR T-cell therapy is one of the newest and most cutting-edge therapies for patients with refractory multiple myeloma. Access to this therapy has been limited throughout the country. However, as shown by our case, this life-saving treatment is now available to patients within the VA. According to a retrospective study on P-RMM patients, the OS in patients who received B-cell maturation antigen (BCMA) targeted therapy was significantly higher than in those who did not (17 vs. 6 months, p < 0.0001). Among the BCMA-targeted therapies, CAR T-cell therapy is associated with the highest OS (29 months) compared to antibody-drug conjugates and bispecific T-cell engagers (Atrash et al, 2023). Thus, accessibility to CAR T-cell therapy was essential in our patient with P-RMM in ensuring her best survival outcomes.