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ASCT may cure follicular lymphoma for some rituximab-naive patients
Prompt autologous stem cell transplantation (ASCT) is often curative in rituximab-naive patients with follicular lymphoma who have experienced early failure of first-line therapy and achieved a response to second-line therapy, suggest results from a registry-based study conducted by GELTAMO (the Spanish Lymphoma and Bone Marrow Transplant Group).
“Overall, our results suggest that, whereas some patients might benefit from more aggressive therapies, such as allogenic stem cell transplantations, or novel drugs, such as immunomodulatory agents, monoclonal antibodies, phosphoinositide 3-kinase inhibitors, or even the application of bispecific T-cell engagers and chimeric antigen receptor T cells, there are a considerable number of patients in this high-risk [early therapy failure] subgroup that can be cured with ASCT, even in the absence of rituximab,” Ana Jiménez-Ubieto, MD, PhD, of the Hospital Universitario, 12 de Octubre, Madrid, Spain, and colleagues wrote.
The results are more favorable when ASCT is performed in patients experiencing early therapy failure, with less than 1 year from first relapse after primary treatment to ASCT.
“Early ASCT could be a hopeful option in patients with difficult access to rituximab,” the researchers wrote in Hematology/Oncology and Stem Cell Therapy.
Patients with follicular lymphoma who experience relapse or progression during or soon after first-line therapy have poor overall survival, and there is no standard therapy for this population, according to the researchers. Previous research has shown that ASCT prolongs survival in those who have received rituximab before transplantation, but benefit in the absence of this agent is unknown.
Dr. Jiménez-Ubieto and colleagues conducted a multicenter registry-based retrospective cohort study of 134 patients with nontransformed follicular lymphoma who underwent ASCT during 1989-2007 while in second complete or partial response to rescue chemotherapy and had not received rituximab.
Overall, 65% of the patients had experienced early therapy failure (relapse or progression within 2 years of starting first-line chemotherapy). Within this group, 78% underwent ASCT within 1 year, and 67% underwent ASCT while in second complete response. Median posttransplantation follow-up for the entire study cohort was 13.4 years.
Study results showed that patients who had experienced early therapy failure versus who had not had poorer 5-year progression-free survival (43% vs. 57%; P = .048) but similar 5-year overall survival (69% vs. 77%; P = .4). However, those patients with early therapy failure who underwent ASCT within 1 year had a statistically indistinguishable 5-year progression-free survival relative to counterparts without early therapy failure (48% vs. 66%; P = .44).
Additionally, the 48% progression-free survival seen in this subset was almost identical to the 49% seen in a historical cohort of patients with early therapy failure who similarly underwent ASCT within 1 year of first relapse but received rituximab before transplantation (Hematol Oncol. 2018;36[5]:765-72). This suggests “that the possible synergistic effect of rituximab plus ASCT is not as relevant if ASCT is offered soon in the course of the disease,” the researchers wrote.
Patients who had experienced early therapy failure achieved better overall survival if they underwent ASCT while in second complete response, as opposed to second partial response. Notably, 56% of those who underwent ASCT while in second complete response were alive at 13.7 years of follow-up and remained so long term.
The study was funded by the Foundation Research Institute at the Hospital Universitario 12 de Octubre. The researchers reported having no relevant conflicts of interest.
SOURCE: Jiménez-Ubieto A et al. Hematol Oncol Stem Cell Ther. 2019 Jul 9. doi: 10.1016/j.hemonc.2019.06.001.
Prompt autologous stem cell transplantation (ASCT) is often curative in rituximab-naive patients with follicular lymphoma who have experienced early failure of first-line therapy and achieved a response to second-line therapy, suggest results from a registry-based study conducted by GELTAMO (the Spanish Lymphoma and Bone Marrow Transplant Group).
“Overall, our results suggest that, whereas some patients might benefit from more aggressive therapies, such as allogenic stem cell transplantations, or novel drugs, such as immunomodulatory agents, monoclonal antibodies, phosphoinositide 3-kinase inhibitors, or even the application of bispecific T-cell engagers and chimeric antigen receptor T cells, there are a considerable number of patients in this high-risk [early therapy failure] subgroup that can be cured with ASCT, even in the absence of rituximab,” Ana Jiménez-Ubieto, MD, PhD, of the Hospital Universitario, 12 de Octubre, Madrid, Spain, and colleagues wrote.
The results are more favorable when ASCT is performed in patients experiencing early therapy failure, with less than 1 year from first relapse after primary treatment to ASCT.
“Early ASCT could be a hopeful option in patients with difficult access to rituximab,” the researchers wrote in Hematology/Oncology and Stem Cell Therapy.
Patients with follicular lymphoma who experience relapse or progression during or soon after first-line therapy have poor overall survival, and there is no standard therapy for this population, according to the researchers. Previous research has shown that ASCT prolongs survival in those who have received rituximab before transplantation, but benefit in the absence of this agent is unknown.
Dr. Jiménez-Ubieto and colleagues conducted a multicenter registry-based retrospective cohort study of 134 patients with nontransformed follicular lymphoma who underwent ASCT during 1989-2007 while in second complete or partial response to rescue chemotherapy and had not received rituximab.
Overall, 65% of the patients had experienced early therapy failure (relapse or progression within 2 years of starting first-line chemotherapy). Within this group, 78% underwent ASCT within 1 year, and 67% underwent ASCT while in second complete response. Median posttransplantation follow-up for the entire study cohort was 13.4 years.
Study results showed that patients who had experienced early therapy failure versus who had not had poorer 5-year progression-free survival (43% vs. 57%; P = .048) but similar 5-year overall survival (69% vs. 77%; P = .4). However, those patients with early therapy failure who underwent ASCT within 1 year had a statistically indistinguishable 5-year progression-free survival relative to counterparts without early therapy failure (48% vs. 66%; P = .44).
Additionally, the 48% progression-free survival seen in this subset was almost identical to the 49% seen in a historical cohort of patients with early therapy failure who similarly underwent ASCT within 1 year of first relapse but received rituximab before transplantation (Hematol Oncol. 2018;36[5]:765-72). This suggests “that the possible synergistic effect of rituximab plus ASCT is not as relevant if ASCT is offered soon in the course of the disease,” the researchers wrote.
Patients who had experienced early therapy failure achieved better overall survival if they underwent ASCT while in second complete response, as opposed to second partial response. Notably, 56% of those who underwent ASCT while in second complete response were alive at 13.7 years of follow-up and remained so long term.
The study was funded by the Foundation Research Institute at the Hospital Universitario 12 de Octubre. The researchers reported having no relevant conflicts of interest.
SOURCE: Jiménez-Ubieto A et al. Hematol Oncol Stem Cell Ther. 2019 Jul 9. doi: 10.1016/j.hemonc.2019.06.001.
Prompt autologous stem cell transplantation (ASCT) is often curative in rituximab-naive patients with follicular lymphoma who have experienced early failure of first-line therapy and achieved a response to second-line therapy, suggest results from a registry-based study conducted by GELTAMO (the Spanish Lymphoma and Bone Marrow Transplant Group).
“Overall, our results suggest that, whereas some patients might benefit from more aggressive therapies, such as allogenic stem cell transplantations, or novel drugs, such as immunomodulatory agents, monoclonal antibodies, phosphoinositide 3-kinase inhibitors, or even the application of bispecific T-cell engagers and chimeric antigen receptor T cells, there are a considerable number of patients in this high-risk [early therapy failure] subgroup that can be cured with ASCT, even in the absence of rituximab,” Ana Jiménez-Ubieto, MD, PhD, of the Hospital Universitario, 12 de Octubre, Madrid, Spain, and colleagues wrote.
The results are more favorable when ASCT is performed in patients experiencing early therapy failure, with less than 1 year from first relapse after primary treatment to ASCT.
“Early ASCT could be a hopeful option in patients with difficult access to rituximab,” the researchers wrote in Hematology/Oncology and Stem Cell Therapy.
Patients with follicular lymphoma who experience relapse or progression during or soon after first-line therapy have poor overall survival, and there is no standard therapy for this population, according to the researchers. Previous research has shown that ASCT prolongs survival in those who have received rituximab before transplantation, but benefit in the absence of this agent is unknown.
Dr. Jiménez-Ubieto and colleagues conducted a multicenter registry-based retrospective cohort study of 134 patients with nontransformed follicular lymphoma who underwent ASCT during 1989-2007 while in second complete or partial response to rescue chemotherapy and had not received rituximab.
Overall, 65% of the patients had experienced early therapy failure (relapse or progression within 2 years of starting first-line chemotherapy). Within this group, 78% underwent ASCT within 1 year, and 67% underwent ASCT while in second complete response. Median posttransplantation follow-up for the entire study cohort was 13.4 years.
Study results showed that patients who had experienced early therapy failure versus who had not had poorer 5-year progression-free survival (43% vs. 57%; P = .048) but similar 5-year overall survival (69% vs. 77%; P = .4). However, those patients with early therapy failure who underwent ASCT within 1 year had a statistically indistinguishable 5-year progression-free survival relative to counterparts without early therapy failure (48% vs. 66%; P = .44).
Additionally, the 48% progression-free survival seen in this subset was almost identical to the 49% seen in a historical cohort of patients with early therapy failure who similarly underwent ASCT within 1 year of first relapse but received rituximab before transplantation (Hematol Oncol. 2018;36[5]:765-72). This suggests “that the possible synergistic effect of rituximab plus ASCT is not as relevant if ASCT is offered soon in the course of the disease,” the researchers wrote.
Patients who had experienced early therapy failure achieved better overall survival if they underwent ASCT while in second complete response, as opposed to second partial response. Notably, 56% of those who underwent ASCT while in second complete response were alive at 13.7 years of follow-up and remained so long term.
The study was funded by the Foundation Research Institute at the Hospital Universitario 12 de Octubre. The researchers reported having no relevant conflicts of interest.
SOURCE: Jiménez-Ubieto A et al. Hematol Oncol Stem Cell Ther. 2019 Jul 9. doi: 10.1016/j.hemonc.2019.06.001.
FROM HEMATOLOGY/ONCOLOGY AND STEM CELL THERAPY
CAR T-cell therapy found safe, effective for HIV-associated lymphoma
HIV positivity does not preclude chimeric antigen receptor (CAR) T-cell therapy for patients with aggressive lymphoma, a report of two cases suggests. Both of the HIV-positive patients, one of whom had long-term psychiatric comorbidity, achieved durable remission on axicabtagene ciloleucel (Yescarta) without undue toxicity.
“To our knowledge, these are the first reported cases of CAR T-cell therapy administered to HIV-infected patients with lymphoma,” Jeremy S. Abramson, MD, of Massachusetts General Hospital, Boston and his colleagues wrote in Cancer. “Patients with HIV and AIDS, as well as those with preexisting mental illness, should not be considered disqualified from CAR T-cell therapy and deserve ongoing studies to optimize efficacy and safety in this population.”
The Food and Drug Administration has approved two CAR T-cell products that target the B-cell antigen CD19 for the treatment of refractory lymphoma. But their efficacy and safety in HIV-positive patients are unknown because this group has been excluded from pivotal clinical trials.
Dr. Abramson and coauthors detail the two cases of successful anti-CD19 CAR T-cell therapy with axicabtagene ciloleucel in patients with HIV-associated, refractory, high-grade B-cell lymphoma.
The first patient was an HIV-positive man with diffuse large B-cell lymphoma (DLBCL) of germinal center B-cell subtype who was intermittently adherent to antiretroviral therapy. His comorbidities included posttraumatic stress disorder and schizoaffective disorder.
Previous treatments for DLBCL included dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R), and rituximab, ifosfamide, carboplatin, and etoposide (RICE). A recurrence precluded high-dose chemotherapy with autologous stem cell support.
With close multidisciplinary management, including psychiatric consultation, the patient became a candidate for CAR T-cell therapy and received axicabtagene ciloleucel. He experienced grade 2 cytokine release syndrome and grade 3 neurologic toxicity, both of which resolved with treatment. Imaging showed complete remission at approximately 3 months that was sustained at 1 year. Additionally, he had an undetectable HIV viral load and was psychiatrically stable.
The second patient was a man with AIDS-associated, non–germinal center B-cell, Epstein-Barr virus–positive DLBCL who was adherent to antiretroviral therapy. His lymphoma had recurred rapidly after initially responding to dose-adjusted EPOCH-R and then was refractory to combination rituximab and lenalidomide. He previously had hepatitis B virus, cytomegalovirus, and Mycobacterium avium complex infections.
Because of prolonged cytopenias and infectious complications after the previous lymphoma treatments, the patient was considered a poor candidate for high-dose chemotherapy. He underwent CAR T-cell therapy with axicabtagene ciloleucel and had a complete remission on day 28. Additionally, his HIV infection remained well controlled.
“Although much remains to be learned regarding CAR T-cell therapy in patients with refractory hematologic malignancies, with or without HIV infection, the cases presented herein demonstrate that patients with chemotherapy-refractory, high-grade B-cell lymphoma can successfully undergo autologous CAR T-cell manufacturing, and subsequently can safely tolerate CAR T-cell therapy and achieve a durable complete remission,” the researchers wrote. “These cases have further demonstrated the proactive, multidisciplinary care required to navigate a patient with high-risk lymphoma through CAR T-cell therapy with attention to significant medical and psychiatric comorbidities.”
Dr. Abramson reported that he has acted as a paid member of the scientific advisory board and as a paid consultant for Kite Pharma, which markets Yescarta, and several other companies.
SOURCE: Abramson JS et al. Cancer. 2019 Sep 10. doi: 10.1002/cncr.32411.
HIV positivity does not preclude chimeric antigen receptor (CAR) T-cell therapy for patients with aggressive lymphoma, a report of two cases suggests. Both of the HIV-positive patients, one of whom had long-term psychiatric comorbidity, achieved durable remission on axicabtagene ciloleucel (Yescarta) without undue toxicity.
“To our knowledge, these are the first reported cases of CAR T-cell therapy administered to HIV-infected patients with lymphoma,” Jeremy S. Abramson, MD, of Massachusetts General Hospital, Boston and his colleagues wrote in Cancer. “Patients with HIV and AIDS, as well as those with preexisting mental illness, should not be considered disqualified from CAR T-cell therapy and deserve ongoing studies to optimize efficacy and safety in this population.”
The Food and Drug Administration has approved two CAR T-cell products that target the B-cell antigen CD19 for the treatment of refractory lymphoma. But their efficacy and safety in HIV-positive patients are unknown because this group has been excluded from pivotal clinical trials.
Dr. Abramson and coauthors detail the two cases of successful anti-CD19 CAR T-cell therapy with axicabtagene ciloleucel in patients with HIV-associated, refractory, high-grade B-cell lymphoma.
The first patient was an HIV-positive man with diffuse large B-cell lymphoma (DLBCL) of germinal center B-cell subtype who was intermittently adherent to antiretroviral therapy. His comorbidities included posttraumatic stress disorder and schizoaffective disorder.
Previous treatments for DLBCL included dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R), and rituximab, ifosfamide, carboplatin, and etoposide (RICE). A recurrence precluded high-dose chemotherapy with autologous stem cell support.
With close multidisciplinary management, including psychiatric consultation, the patient became a candidate for CAR T-cell therapy and received axicabtagene ciloleucel. He experienced grade 2 cytokine release syndrome and grade 3 neurologic toxicity, both of which resolved with treatment. Imaging showed complete remission at approximately 3 months that was sustained at 1 year. Additionally, he had an undetectable HIV viral load and was psychiatrically stable.
The second patient was a man with AIDS-associated, non–germinal center B-cell, Epstein-Barr virus–positive DLBCL who was adherent to antiretroviral therapy. His lymphoma had recurred rapidly after initially responding to dose-adjusted EPOCH-R and then was refractory to combination rituximab and lenalidomide. He previously had hepatitis B virus, cytomegalovirus, and Mycobacterium avium complex infections.
Because of prolonged cytopenias and infectious complications after the previous lymphoma treatments, the patient was considered a poor candidate for high-dose chemotherapy. He underwent CAR T-cell therapy with axicabtagene ciloleucel and had a complete remission on day 28. Additionally, his HIV infection remained well controlled.
“Although much remains to be learned regarding CAR T-cell therapy in patients with refractory hematologic malignancies, with or without HIV infection, the cases presented herein demonstrate that patients with chemotherapy-refractory, high-grade B-cell lymphoma can successfully undergo autologous CAR T-cell manufacturing, and subsequently can safely tolerate CAR T-cell therapy and achieve a durable complete remission,” the researchers wrote. “These cases have further demonstrated the proactive, multidisciplinary care required to navigate a patient with high-risk lymphoma through CAR T-cell therapy with attention to significant medical and psychiatric comorbidities.”
Dr. Abramson reported that he has acted as a paid member of the scientific advisory board and as a paid consultant for Kite Pharma, which markets Yescarta, and several other companies.
SOURCE: Abramson JS et al. Cancer. 2019 Sep 10. doi: 10.1002/cncr.32411.
HIV positivity does not preclude chimeric antigen receptor (CAR) T-cell therapy for patients with aggressive lymphoma, a report of two cases suggests. Both of the HIV-positive patients, one of whom had long-term psychiatric comorbidity, achieved durable remission on axicabtagene ciloleucel (Yescarta) without undue toxicity.
“To our knowledge, these are the first reported cases of CAR T-cell therapy administered to HIV-infected patients with lymphoma,” Jeremy S. Abramson, MD, of Massachusetts General Hospital, Boston and his colleagues wrote in Cancer. “Patients with HIV and AIDS, as well as those with preexisting mental illness, should not be considered disqualified from CAR T-cell therapy and deserve ongoing studies to optimize efficacy and safety in this population.”
The Food and Drug Administration has approved two CAR T-cell products that target the B-cell antigen CD19 for the treatment of refractory lymphoma. But their efficacy and safety in HIV-positive patients are unknown because this group has been excluded from pivotal clinical trials.
Dr. Abramson and coauthors detail the two cases of successful anti-CD19 CAR T-cell therapy with axicabtagene ciloleucel in patients with HIV-associated, refractory, high-grade B-cell lymphoma.
The first patient was an HIV-positive man with diffuse large B-cell lymphoma (DLBCL) of germinal center B-cell subtype who was intermittently adherent to antiretroviral therapy. His comorbidities included posttraumatic stress disorder and schizoaffective disorder.
Previous treatments for DLBCL included dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R), and rituximab, ifosfamide, carboplatin, and etoposide (RICE). A recurrence precluded high-dose chemotherapy with autologous stem cell support.
With close multidisciplinary management, including psychiatric consultation, the patient became a candidate for CAR T-cell therapy and received axicabtagene ciloleucel. He experienced grade 2 cytokine release syndrome and grade 3 neurologic toxicity, both of which resolved with treatment. Imaging showed complete remission at approximately 3 months that was sustained at 1 year. Additionally, he had an undetectable HIV viral load and was psychiatrically stable.
The second patient was a man with AIDS-associated, non–germinal center B-cell, Epstein-Barr virus–positive DLBCL who was adherent to antiretroviral therapy. His lymphoma had recurred rapidly after initially responding to dose-adjusted EPOCH-R and then was refractory to combination rituximab and lenalidomide. He previously had hepatitis B virus, cytomegalovirus, and Mycobacterium avium complex infections.
Because of prolonged cytopenias and infectious complications after the previous lymphoma treatments, the patient was considered a poor candidate for high-dose chemotherapy. He underwent CAR T-cell therapy with axicabtagene ciloleucel and had a complete remission on day 28. Additionally, his HIV infection remained well controlled.
“Although much remains to be learned regarding CAR T-cell therapy in patients with refractory hematologic malignancies, with or without HIV infection, the cases presented herein demonstrate that patients with chemotherapy-refractory, high-grade B-cell lymphoma can successfully undergo autologous CAR T-cell manufacturing, and subsequently can safely tolerate CAR T-cell therapy and achieve a durable complete remission,” the researchers wrote. “These cases have further demonstrated the proactive, multidisciplinary care required to navigate a patient with high-risk lymphoma through CAR T-cell therapy with attention to significant medical and psychiatric comorbidities.”
Dr. Abramson reported that he has acted as a paid member of the scientific advisory board and as a paid consultant for Kite Pharma, which markets Yescarta, and several other companies.
SOURCE: Abramson JS et al. Cancer. 2019 Sep 10. doi: 10.1002/cncr.32411.
FROM CANCER
Staging PET/CT better defines extent of mantle cell lymphoma
Use of staging PET/CT better defines the extent of mantle cell lymphoma (MCL) in certain compartments, adding important information for treatment decisions, a cohort study suggests. However, patient selection and evaluation criteria are important for its utility.
“A correct and early identification of initial disease could be crucial because it could affect patient management and therapeutic choice,” Domenico Albano, MD, a nuclear medicine physician at the University of Brescia (Italy) and Spedali Civili Brescia, and colleagues wrote in Clinical Lymphoma, Myeloma, & Leukemia.
Using retrospective data from two centers and 122 patients with MCL, the investigators compared the utility of staging 18F-fluorodeoxyglucose (18F-FDG) PET/CT with that of other modalities used for detecting disease in specific compartments. They also assessed its impact on patient management.
The study results showed that, with the exception of a single patient having bone marrow involvement, all patients had positive PET/CT results, with detection of at least one hypermetabolic lesion.
For assessing nodal involvement, compared with CT alone, PET/CT detected additional lesions in 21% of patients. Splenic lesions were detected by PET/CT in 49% of patients and by CT alone in 47%.
For assessing bone marrow involvement, compared with bone marrow biopsy, PET/CT had a sensitivity of 52%, a specificity of 98%, a positive predictive value of 97%, a negative predictive value of 65%, and an overall accuracy of 74%.
For gastrointestinal involvement, compared with endoscopy, PET/CT had a sensitivity of 64% (78% after excluding diabetic patients taking metformin), a specificity of 91% (92%), a positive predictive value of 69% (72%), a negative predictive value of 90% (94%), and an overall accuracy of 85% (89%).
Ultimately, relative to CT alone, PET/CT altered stage and management in 19% of patients. Specifically, this imaging led to up-staging in 17% of patients, prompting clinicians to switch to more-aggressive chemotherapy, and down-staging in 2% of patients, prompting clinicians to skip unnecessary invasive therapies.
“We demonstrated that 18F-FDG pathologic uptake in MCL occurred in almost all patients, with excellent detection rate in nodal and splenic disease – indeed, better than CT,” the researchers wrote. “When we analyzed bone marrow and gastrointestinal involvement, the selection of patients excluding all conditions potentially affecting organ uptake and the use of specific criteria for the evaluation of these organs seemed to be crucial. Within these caveats, PET/CT showed good specificity for bone marrow and gastrointestinal evaluation.”
Study funding was not disclosed. Dr. Albano reported having no relevant conflicts of interest.
SOURCE: Albano D et al. Clin Lymphoma Myeloma Leuk. 2019 Aug;19(8):e457-64.
Use of staging PET/CT better defines the extent of mantle cell lymphoma (MCL) in certain compartments, adding important information for treatment decisions, a cohort study suggests. However, patient selection and evaluation criteria are important for its utility.
“A correct and early identification of initial disease could be crucial because it could affect patient management and therapeutic choice,” Domenico Albano, MD, a nuclear medicine physician at the University of Brescia (Italy) and Spedali Civili Brescia, and colleagues wrote in Clinical Lymphoma, Myeloma, & Leukemia.
Using retrospective data from two centers and 122 patients with MCL, the investigators compared the utility of staging 18F-fluorodeoxyglucose (18F-FDG) PET/CT with that of other modalities used for detecting disease in specific compartments. They also assessed its impact on patient management.
The study results showed that, with the exception of a single patient having bone marrow involvement, all patients had positive PET/CT results, with detection of at least one hypermetabolic lesion.
For assessing nodal involvement, compared with CT alone, PET/CT detected additional lesions in 21% of patients. Splenic lesions were detected by PET/CT in 49% of patients and by CT alone in 47%.
For assessing bone marrow involvement, compared with bone marrow biopsy, PET/CT had a sensitivity of 52%, a specificity of 98%, a positive predictive value of 97%, a negative predictive value of 65%, and an overall accuracy of 74%.
For gastrointestinal involvement, compared with endoscopy, PET/CT had a sensitivity of 64% (78% after excluding diabetic patients taking metformin), a specificity of 91% (92%), a positive predictive value of 69% (72%), a negative predictive value of 90% (94%), and an overall accuracy of 85% (89%).
Ultimately, relative to CT alone, PET/CT altered stage and management in 19% of patients. Specifically, this imaging led to up-staging in 17% of patients, prompting clinicians to switch to more-aggressive chemotherapy, and down-staging in 2% of patients, prompting clinicians to skip unnecessary invasive therapies.
“We demonstrated that 18F-FDG pathologic uptake in MCL occurred in almost all patients, with excellent detection rate in nodal and splenic disease – indeed, better than CT,” the researchers wrote. “When we analyzed bone marrow and gastrointestinal involvement, the selection of patients excluding all conditions potentially affecting organ uptake and the use of specific criteria for the evaluation of these organs seemed to be crucial. Within these caveats, PET/CT showed good specificity for bone marrow and gastrointestinal evaluation.”
Study funding was not disclosed. Dr. Albano reported having no relevant conflicts of interest.
SOURCE: Albano D et al. Clin Lymphoma Myeloma Leuk. 2019 Aug;19(8):e457-64.
Use of staging PET/CT better defines the extent of mantle cell lymphoma (MCL) in certain compartments, adding important information for treatment decisions, a cohort study suggests. However, patient selection and evaluation criteria are important for its utility.
“A correct and early identification of initial disease could be crucial because it could affect patient management and therapeutic choice,” Domenico Albano, MD, a nuclear medicine physician at the University of Brescia (Italy) and Spedali Civili Brescia, and colleagues wrote in Clinical Lymphoma, Myeloma, & Leukemia.
Using retrospective data from two centers and 122 patients with MCL, the investigators compared the utility of staging 18F-fluorodeoxyglucose (18F-FDG) PET/CT with that of other modalities used for detecting disease in specific compartments. They also assessed its impact on patient management.
The study results showed that, with the exception of a single patient having bone marrow involvement, all patients had positive PET/CT results, with detection of at least one hypermetabolic lesion.
For assessing nodal involvement, compared with CT alone, PET/CT detected additional lesions in 21% of patients. Splenic lesions were detected by PET/CT in 49% of patients and by CT alone in 47%.
For assessing bone marrow involvement, compared with bone marrow biopsy, PET/CT had a sensitivity of 52%, a specificity of 98%, a positive predictive value of 97%, a negative predictive value of 65%, and an overall accuracy of 74%.
For gastrointestinal involvement, compared with endoscopy, PET/CT had a sensitivity of 64% (78% after excluding diabetic patients taking metformin), a specificity of 91% (92%), a positive predictive value of 69% (72%), a negative predictive value of 90% (94%), and an overall accuracy of 85% (89%).
Ultimately, relative to CT alone, PET/CT altered stage and management in 19% of patients. Specifically, this imaging led to up-staging in 17% of patients, prompting clinicians to switch to more-aggressive chemotherapy, and down-staging in 2% of patients, prompting clinicians to skip unnecessary invasive therapies.
“We demonstrated that 18F-FDG pathologic uptake in MCL occurred in almost all patients, with excellent detection rate in nodal and splenic disease – indeed, better than CT,” the researchers wrote. “When we analyzed bone marrow and gastrointestinal involvement, the selection of patients excluding all conditions potentially affecting organ uptake and the use of specific criteria for the evaluation of these organs seemed to be crucial. Within these caveats, PET/CT showed good specificity for bone marrow and gastrointestinal evaluation.”
Study funding was not disclosed. Dr. Albano reported having no relevant conflicts of interest.
SOURCE: Albano D et al. Clin Lymphoma Myeloma Leuk. 2019 Aug;19(8):e457-64.
FROM CLINICAL LYMPHOMA, MYELOMA, & LEUKEMIA
Could home care replace inpatient HSCT?
Can receiving all posttransplant care at home benefit patients undergoing hematopoietic stem cell transplant (HSCT)? Researchers are conducting phase 2 trials to find out.
Nelson Chao, MD, and colleagues at Duke University in Durham, N.C., completed a phase 1 trial that suggested post-HSCT care at home was feasible and safe (Blood. 2017;130:745).
Now, the team is conducting phase 2 trials – NCT01725022 and NCT02218151 – comparing patients who receive all posttransplant care at home with patients treated in the hospital or in the outpatient setting with daily visits to the clinic.
The main goal is to determine if allogeneic HSCT recipients treated at home can maintain their normal microbiome and, as a result, have a lower risk of graft-versus-host disease (GVHD). The researchers are also looking at other outcomes such as quality of life, treatment-related morbidities and mortality, and the cost of care for both allogeneic and autologous transplant recipients.
To be eligible for home care after HSCT, a patient must live within a 90-minute driving distance of Duke and have a caregiver available at home. The patient’s home must pass an inspection, showing it to be free of sources for potential infection, such as mold or pets that sleep in the patient’s bed.
When the time comes for treatment, the patient receives conditioning at the hospital but can return home the day before or the day of transplant. After discharge, the patient is visited by a nurse practitioner or physician assistant each morning for a physical examination and blood draw.
In the afternoon, the patient is visited by a clinic nurse who brings any necessary supplies or treatments, such as blood products or intravenous antibiotics. The patient also has daily video calls with an attending physician and can be admitted to the hospital for any events that cannot be managed in the home setting.
Patients can have visitors and spend time away from home, but precautions are necessary. Friends or family who are sick should not be allowed to visit, and patients should avoid crowds when they go out.
Initial findings
The Duke team has treated 41 HSCT recipients at home so far. Dr. Chao said it’s still too early to draw any conclusions about differences in outcomes between home care and inpatient/outpatient HSCT.
However, a preliminary analysis of costs suggests home care is cheaper than inpatient HSCT. The researchers found that, for the first several transplants, at day 60, the cost of home care was roughly half that of inpatient HSCT.
In addition, patients seem to be happy with posttransplant care at home.
“The patients love being at home, in their own environment, with their families,” Dr. Chao said. “Almost every single patient [in the phase 1 trial] said that he or she liked it much better. There was one patient in the phase 1 that felt a little isolated, and I can see why because we say, ‘You can stay home, but don’t have a whole lot of people in.’ ”
One patient’s experience
Beth Vanderkin said it was “a blessing” to receive care at home after undergoing HSCT at Duke.
Ms. Vanderkin was diagnosed with diffuse large B-cell lymphoma in 2014. After two chemotherapy regimens failed to shrink the tumor in her chest, she underwent radiotherapy and responded well. When a PET scan revealed the tumor had gone completely, she proceeded to transplant.
She received a haploidentical HSCT using cells donated by her eldest daughter, Hannah Eichhorst. Ms. Vanderkin received the transplant in the hospital, and for 2 weeks after that, she made daily visits to the transplant clinic.
After those 2 weeks, Ms. Vanderkin continued her treatment at home. Like other patients eligible for home care, Ms. Vanderkin lived close to Duke, had a caregiver available, and had passed a home inspection. The Duke team shipped the needed medical supplies to her house and arranged twice-daily visits from nurses and daily video calls with a doctor.
Ms. Vanderkin said receiving care at home was “a game changer.” She derived comfort from recovering in her own environment, could spend more time with her family, and didn’t have to miss special events. While receiving care at home, Ms. Vanderkin attended the homecoming event where her son, Josiah, was part of the court. Wearing a face mask and carrying a portable pump in her purse, Ms. Vanderkin joined other mothers in escorting their children onto the football field.
“I got to escort my son out onto the field, and he was crowned king that night,” Ms. Vanderkin said. “I didn’t do a lot of things [while receiving care at home], but there were things I didn’t have to miss because I was at home and not in the hospital.”
Ms. Vanderkin said home care was also beneficial for her husband, who was her caregiver. Thomas Vanderkin was able to work from home while caring for his wife, and the daily nurses’ visits allowed him to run errands without having to leave Ms. Vanderkin alone.
Since her experience with home care, Ms. Vanderkin has spent many more days in the hospital and clinic. She experienced a relapse after the transplant and went on to receive more chemotherapy as well as ipilimumab. She responded to that treatment and has now been cancer-free for 3 years.
The ipilimumab did cause side effects, including intestinal problems that resulted in the need for parenteral nutrition. This side effect was made more bearable, Ms. Vanderkin said, because she was able to receive the parenteral nutrition at home. She and her husband were comfortable with additional home care because of their positive experience with posttransplant care.
“I think we’re conditioned to think that, to receive the best care, we have to be sitting in a hospital room or a clinic, but I think there’s a lot of things we can probably do at home,” Ms. Vanderkin said. “And we might fare a lot better as patients if we’re in an environment that we feel comfortable in.”
Experience at other centers
The team at Duke is not the first to study HSCT care at home. In fact, researchers in Sweden have been studying posttransplant home care since 1998.
A pilot trial the group published in 2000 suggested that home care was safe and, in some ways, superior to inpatient HSCT (Bone Marrow Transplant. 2000 Nov;26[10]:1057-60). Patients treated at home had a lower rate of bacteremia, fewer days of total parenteral nutrition, fewer erythrocyte transfusions, and fewer days on antibiotics and analgesics. Rates of fever, engraftment time, and acute GVHD were similar between the inpatient and home-care groups.
A study published by the same researchers in 2002 showed that patients who received home care had lower rates of grade 2-4 acute GVHD and transplant-related mortality compared to inpatients (Blood. 2002 Dec 15;100[13]:4317-24). Two-year overall survival was superior with home care as well.
On the other hand, a study the group published in 2013 showed no significant differences in 5-year survival, transplant-related mortality, relapse, or chronic GVHD between inpatients and those who received care at home (Biol Blood Marrow Transplant. 2013. doi: 10.1016/j.bbmt.2012.11.5189).
The phase 2 trials at Duke should provide more insight into patient outcomes, but results probably won’t be available for 2 more years, Dr. Chao said.
In the meantime, other U.S. researchers are studying home care as well. Memorial Sloan Kettering Cancer Center is conducting a pilot study to determine if HSCT care at home is feasible (NCT02671448).
Dr. Chao said home care should be possible for other centers, particularly those that already perform outpatient HSCT.
“Having the outpatient infrastructure to support these patients is a big step,” he said. “And I think we were able to do that mainly because we do most of our transplants in the outpatient setting already. So that jump to the home is a little less compared to a center that does no outpatient transplants.”
He added, “There’s a certain amount of inertia to overcome and a certain amount of apprehension from the caregivers initially because [patients aren’t] sitting in your unit all the time, but I don’t see this as a huge barrier.”
In fact, Dr. Chao said, if results with home care are favorable, it could potentially replace inpatient HSCT for certain patients.
Dr. Chao’s research is supported by Duke University, and he reported having no relevant financial disclosures.
Can receiving all posttransplant care at home benefit patients undergoing hematopoietic stem cell transplant (HSCT)? Researchers are conducting phase 2 trials to find out.
Nelson Chao, MD, and colleagues at Duke University in Durham, N.C., completed a phase 1 trial that suggested post-HSCT care at home was feasible and safe (Blood. 2017;130:745).
Now, the team is conducting phase 2 trials – NCT01725022 and NCT02218151 – comparing patients who receive all posttransplant care at home with patients treated in the hospital or in the outpatient setting with daily visits to the clinic.
The main goal is to determine if allogeneic HSCT recipients treated at home can maintain their normal microbiome and, as a result, have a lower risk of graft-versus-host disease (GVHD). The researchers are also looking at other outcomes such as quality of life, treatment-related morbidities and mortality, and the cost of care for both allogeneic and autologous transplant recipients.
To be eligible for home care after HSCT, a patient must live within a 90-minute driving distance of Duke and have a caregiver available at home. The patient’s home must pass an inspection, showing it to be free of sources for potential infection, such as mold or pets that sleep in the patient’s bed.
When the time comes for treatment, the patient receives conditioning at the hospital but can return home the day before or the day of transplant. After discharge, the patient is visited by a nurse practitioner or physician assistant each morning for a physical examination and blood draw.
In the afternoon, the patient is visited by a clinic nurse who brings any necessary supplies or treatments, such as blood products or intravenous antibiotics. The patient also has daily video calls with an attending physician and can be admitted to the hospital for any events that cannot be managed in the home setting.
Patients can have visitors and spend time away from home, but precautions are necessary. Friends or family who are sick should not be allowed to visit, and patients should avoid crowds when they go out.
Initial findings
The Duke team has treated 41 HSCT recipients at home so far. Dr. Chao said it’s still too early to draw any conclusions about differences in outcomes between home care and inpatient/outpatient HSCT.
However, a preliminary analysis of costs suggests home care is cheaper than inpatient HSCT. The researchers found that, for the first several transplants, at day 60, the cost of home care was roughly half that of inpatient HSCT.
In addition, patients seem to be happy with posttransplant care at home.
“The patients love being at home, in their own environment, with their families,” Dr. Chao said. “Almost every single patient [in the phase 1 trial] said that he or she liked it much better. There was one patient in the phase 1 that felt a little isolated, and I can see why because we say, ‘You can stay home, but don’t have a whole lot of people in.’ ”
One patient’s experience
Beth Vanderkin said it was “a blessing” to receive care at home after undergoing HSCT at Duke.
Ms. Vanderkin was diagnosed with diffuse large B-cell lymphoma in 2014. After two chemotherapy regimens failed to shrink the tumor in her chest, she underwent radiotherapy and responded well. When a PET scan revealed the tumor had gone completely, she proceeded to transplant.
She received a haploidentical HSCT using cells donated by her eldest daughter, Hannah Eichhorst. Ms. Vanderkin received the transplant in the hospital, and for 2 weeks after that, she made daily visits to the transplant clinic.
After those 2 weeks, Ms. Vanderkin continued her treatment at home. Like other patients eligible for home care, Ms. Vanderkin lived close to Duke, had a caregiver available, and had passed a home inspection. The Duke team shipped the needed medical supplies to her house and arranged twice-daily visits from nurses and daily video calls with a doctor.
Ms. Vanderkin said receiving care at home was “a game changer.” She derived comfort from recovering in her own environment, could spend more time with her family, and didn’t have to miss special events. While receiving care at home, Ms. Vanderkin attended the homecoming event where her son, Josiah, was part of the court. Wearing a face mask and carrying a portable pump in her purse, Ms. Vanderkin joined other mothers in escorting their children onto the football field.
“I got to escort my son out onto the field, and he was crowned king that night,” Ms. Vanderkin said. “I didn’t do a lot of things [while receiving care at home], but there were things I didn’t have to miss because I was at home and not in the hospital.”
Ms. Vanderkin said home care was also beneficial for her husband, who was her caregiver. Thomas Vanderkin was able to work from home while caring for his wife, and the daily nurses’ visits allowed him to run errands without having to leave Ms. Vanderkin alone.
Since her experience with home care, Ms. Vanderkin has spent many more days in the hospital and clinic. She experienced a relapse after the transplant and went on to receive more chemotherapy as well as ipilimumab. She responded to that treatment and has now been cancer-free for 3 years.
The ipilimumab did cause side effects, including intestinal problems that resulted in the need for parenteral nutrition. This side effect was made more bearable, Ms. Vanderkin said, because she was able to receive the parenteral nutrition at home. She and her husband were comfortable with additional home care because of their positive experience with posttransplant care.
“I think we’re conditioned to think that, to receive the best care, we have to be sitting in a hospital room or a clinic, but I think there’s a lot of things we can probably do at home,” Ms. Vanderkin said. “And we might fare a lot better as patients if we’re in an environment that we feel comfortable in.”
Experience at other centers
The team at Duke is not the first to study HSCT care at home. In fact, researchers in Sweden have been studying posttransplant home care since 1998.
A pilot trial the group published in 2000 suggested that home care was safe and, in some ways, superior to inpatient HSCT (Bone Marrow Transplant. 2000 Nov;26[10]:1057-60). Patients treated at home had a lower rate of bacteremia, fewer days of total parenteral nutrition, fewer erythrocyte transfusions, and fewer days on antibiotics and analgesics. Rates of fever, engraftment time, and acute GVHD were similar between the inpatient and home-care groups.
A study published by the same researchers in 2002 showed that patients who received home care had lower rates of grade 2-4 acute GVHD and transplant-related mortality compared to inpatients (Blood. 2002 Dec 15;100[13]:4317-24). Two-year overall survival was superior with home care as well.
On the other hand, a study the group published in 2013 showed no significant differences in 5-year survival, transplant-related mortality, relapse, or chronic GVHD between inpatients and those who received care at home (Biol Blood Marrow Transplant. 2013. doi: 10.1016/j.bbmt.2012.11.5189).
The phase 2 trials at Duke should provide more insight into patient outcomes, but results probably won’t be available for 2 more years, Dr. Chao said.
In the meantime, other U.S. researchers are studying home care as well. Memorial Sloan Kettering Cancer Center is conducting a pilot study to determine if HSCT care at home is feasible (NCT02671448).
Dr. Chao said home care should be possible for other centers, particularly those that already perform outpatient HSCT.
“Having the outpatient infrastructure to support these patients is a big step,” he said. “And I think we were able to do that mainly because we do most of our transplants in the outpatient setting already. So that jump to the home is a little less compared to a center that does no outpatient transplants.”
He added, “There’s a certain amount of inertia to overcome and a certain amount of apprehension from the caregivers initially because [patients aren’t] sitting in your unit all the time, but I don’t see this as a huge barrier.”
In fact, Dr. Chao said, if results with home care are favorable, it could potentially replace inpatient HSCT for certain patients.
Dr. Chao’s research is supported by Duke University, and he reported having no relevant financial disclosures.
Can receiving all posttransplant care at home benefit patients undergoing hematopoietic stem cell transplant (HSCT)? Researchers are conducting phase 2 trials to find out.
Nelson Chao, MD, and colleagues at Duke University in Durham, N.C., completed a phase 1 trial that suggested post-HSCT care at home was feasible and safe (Blood. 2017;130:745).
Now, the team is conducting phase 2 trials – NCT01725022 and NCT02218151 – comparing patients who receive all posttransplant care at home with patients treated in the hospital or in the outpatient setting with daily visits to the clinic.
The main goal is to determine if allogeneic HSCT recipients treated at home can maintain their normal microbiome and, as a result, have a lower risk of graft-versus-host disease (GVHD). The researchers are also looking at other outcomes such as quality of life, treatment-related morbidities and mortality, and the cost of care for both allogeneic and autologous transplant recipients.
To be eligible for home care after HSCT, a patient must live within a 90-minute driving distance of Duke and have a caregiver available at home. The patient’s home must pass an inspection, showing it to be free of sources for potential infection, such as mold or pets that sleep in the patient’s bed.
When the time comes for treatment, the patient receives conditioning at the hospital but can return home the day before or the day of transplant. After discharge, the patient is visited by a nurse practitioner or physician assistant each morning for a physical examination and blood draw.
In the afternoon, the patient is visited by a clinic nurse who brings any necessary supplies or treatments, such as blood products or intravenous antibiotics. The patient also has daily video calls with an attending physician and can be admitted to the hospital for any events that cannot be managed in the home setting.
Patients can have visitors and spend time away from home, but precautions are necessary. Friends or family who are sick should not be allowed to visit, and patients should avoid crowds when they go out.
Initial findings
The Duke team has treated 41 HSCT recipients at home so far. Dr. Chao said it’s still too early to draw any conclusions about differences in outcomes between home care and inpatient/outpatient HSCT.
However, a preliminary analysis of costs suggests home care is cheaper than inpatient HSCT. The researchers found that, for the first several transplants, at day 60, the cost of home care was roughly half that of inpatient HSCT.
In addition, patients seem to be happy with posttransplant care at home.
“The patients love being at home, in their own environment, with their families,” Dr. Chao said. “Almost every single patient [in the phase 1 trial] said that he or she liked it much better. There was one patient in the phase 1 that felt a little isolated, and I can see why because we say, ‘You can stay home, but don’t have a whole lot of people in.’ ”
One patient’s experience
Beth Vanderkin said it was “a blessing” to receive care at home after undergoing HSCT at Duke.
Ms. Vanderkin was diagnosed with diffuse large B-cell lymphoma in 2014. After two chemotherapy regimens failed to shrink the tumor in her chest, she underwent radiotherapy and responded well. When a PET scan revealed the tumor had gone completely, she proceeded to transplant.
She received a haploidentical HSCT using cells donated by her eldest daughter, Hannah Eichhorst. Ms. Vanderkin received the transplant in the hospital, and for 2 weeks after that, she made daily visits to the transplant clinic.
After those 2 weeks, Ms. Vanderkin continued her treatment at home. Like other patients eligible for home care, Ms. Vanderkin lived close to Duke, had a caregiver available, and had passed a home inspection. The Duke team shipped the needed medical supplies to her house and arranged twice-daily visits from nurses and daily video calls with a doctor.
Ms. Vanderkin said receiving care at home was “a game changer.” She derived comfort from recovering in her own environment, could spend more time with her family, and didn’t have to miss special events. While receiving care at home, Ms. Vanderkin attended the homecoming event where her son, Josiah, was part of the court. Wearing a face mask and carrying a portable pump in her purse, Ms. Vanderkin joined other mothers in escorting their children onto the football field.
“I got to escort my son out onto the field, and he was crowned king that night,” Ms. Vanderkin said. “I didn’t do a lot of things [while receiving care at home], but there were things I didn’t have to miss because I was at home and not in the hospital.”
Ms. Vanderkin said home care was also beneficial for her husband, who was her caregiver. Thomas Vanderkin was able to work from home while caring for his wife, and the daily nurses’ visits allowed him to run errands without having to leave Ms. Vanderkin alone.
Since her experience with home care, Ms. Vanderkin has spent many more days in the hospital and clinic. She experienced a relapse after the transplant and went on to receive more chemotherapy as well as ipilimumab. She responded to that treatment and has now been cancer-free for 3 years.
The ipilimumab did cause side effects, including intestinal problems that resulted in the need for parenteral nutrition. This side effect was made more bearable, Ms. Vanderkin said, because she was able to receive the parenteral nutrition at home. She and her husband were comfortable with additional home care because of their positive experience with posttransplant care.
“I think we’re conditioned to think that, to receive the best care, we have to be sitting in a hospital room or a clinic, but I think there’s a lot of things we can probably do at home,” Ms. Vanderkin said. “And we might fare a lot better as patients if we’re in an environment that we feel comfortable in.”
Experience at other centers
The team at Duke is not the first to study HSCT care at home. In fact, researchers in Sweden have been studying posttransplant home care since 1998.
A pilot trial the group published in 2000 suggested that home care was safe and, in some ways, superior to inpatient HSCT (Bone Marrow Transplant. 2000 Nov;26[10]:1057-60). Patients treated at home had a lower rate of bacteremia, fewer days of total parenteral nutrition, fewer erythrocyte transfusions, and fewer days on antibiotics and analgesics. Rates of fever, engraftment time, and acute GVHD were similar between the inpatient and home-care groups.
A study published by the same researchers in 2002 showed that patients who received home care had lower rates of grade 2-4 acute GVHD and transplant-related mortality compared to inpatients (Blood. 2002 Dec 15;100[13]:4317-24). Two-year overall survival was superior with home care as well.
On the other hand, a study the group published in 2013 showed no significant differences in 5-year survival, transplant-related mortality, relapse, or chronic GVHD between inpatients and those who received care at home (Biol Blood Marrow Transplant. 2013. doi: 10.1016/j.bbmt.2012.11.5189).
The phase 2 trials at Duke should provide more insight into patient outcomes, but results probably won’t be available for 2 more years, Dr. Chao said.
In the meantime, other U.S. researchers are studying home care as well. Memorial Sloan Kettering Cancer Center is conducting a pilot study to determine if HSCT care at home is feasible (NCT02671448).
Dr. Chao said home care should be possible for other centers, particularly those that already perform outpatient HSCT.
“Having the outpatient infrastructure to support these patients is a big step,” he said. “And I think we were able to do that mainly because we do most of our transplants in the outpatient setting already. So that jump to the home is a little less compared to a center that does no outpatient transplants.”
He added, “There’s a certain amount of inertia to overcome and a certain amount of apprehension from the caregivers initially because [patients aren’t] sitting in your unit all the time, but I don’t see this as a huge barrier.”
In fact, Dr. Chao said, if results with home care are favorable, it could potentially replace inpatient HSCT for certain patients.
Dr. Chao’s research is supported by Duke University, and he reported having no relevant financial disclosures.
Study confirms prognostic impact of MYC partner gene in DLBCL
MYC rearrangement (MYC-R) has negative prognostic significance in patients with diffuse large B-cell lymphoma (DLBCL) in relation to the MYC partner gene, according to a retrospective study.
The negative prognostic effect of MYC-R was largely limited to patients with MYC–double hit/MYC–triple hit status and an immunoglobulin (IG) partner within 24 months following diagnosis.
“The primary objective of the study was to validate the prognostic relevance of [MYC–single hit] and [MYC–double hit/MYC–triple hit] status within the context of the MYC translocation partner (MYC-IG v. MYC-non-IG) in patients with DLBCL morphology,” wrote Andreas Rosenwald, MD, of the University of Würzburg (Germany) and colleagues in the Journal of Clinical Oncology.
The researchers identified 5,117 patients who all received R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-CHOP–like immunochemotherapy, 2,383 of whom were evaluable for MYC-R and had complete clinical data. The cohort consisted of patients enrolled in various population-based registries and prospective clinical studies throughout North America and Europe.
The team used fluorescence in situ hybridization testing to identify MYC-R, in addition to BCL2 and/or BCL6 translocations if MYC-R was detected. Subsequently, these data were correlated with clinical endpoints.
After analysis, the researchers found that MYC-R was detected in 11% of patients. The presence of MYC-R was associated with significantly reduced survival, particularly within the initial 24 months following diagnosis.
Adverse prognostic implications were largely apparent in patients with accompanying rearrangement of BCL2 and/or BCL6 translocations (MYC–double-hit/MYC–triple hit status) and an immunoglobulin (IG) partner (hazard ratio, 2.4; 95% confidence interval, 1.6-3.6; P less than .001).
“These data suggest that little justification exists for altering initial therapeutic approaches in patients with DLBCL whose tumors carry an MYC translocation alone [MYC single hit],” they wrote. “However, for [MYC double hit/MYC triple hit] DLBCL, the major negative prognostic impact and 2-year effect support the practice of optimizing first-line treatment approaches to achieve maximum complete response rates because salvage treatment at relapse is not effective.”
Dr. Rosenwald and colleagues suggested that, in the future, diagnostic approaches should be implemented to detect patients in this high-risk group and that risk-modified treatment strategies should be further developed.
The study was supported by unrestricted grants to the Lunenburg Lymphoma Biomarker Consortium from several pharmaceutical companies and Bloodwise. Dr. Rosenwald reported having no conflicts of interest, but several coauthors reported relationships with industry.
SOURCE: : Rosenwald A et al. J Clin Oncol. 2019 Sep 9. doi: 10.1200/JCO.19.00743.
MYC rearrangement (MYC-R) has negative prognostic significance in patients with diffuse large B-cell lymphoma (DLBCL) in relation to the MYC partner gene, according to a retrospective study.
The negative prognostic effect of MYC-R was largely limited to patients with MYC–double hit/MYC–triple hit status and an immunoglobulin (IG) partner within 24 months following diagnosis.
“The primary objective of the study was to validate the prognostic relevance of [MYC–single hit] and [MYC–double hit/MYC–triple hit] status within the context of the MYC translocation partner (MYC-IG v. MYC-non-IG) in patients with DLBCL morphology,” wrote Andreas Rosenwald, MD, of the University of Würzburg (Germany) and colleagues in the Journal of Clinical Oncology.
The researchers identified 5,117 patients who all received R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-CHOP–like immunochemotherapy, 2,383 of whom were evaluable for MYC-R and had complete clinical data. The cohort consisted of patients enrolled in various population-based registries and prospective clinical studies throughout North America and Europe.
The team used fluorescence in situ hybridization testing to identify MYC-R, in addition to BCL2 and/or BCL6 translocations if MYC-R was detected. Subsequently, these data were correlated with clinical endpoints.
After analysis, the researchers found that MYC-R was detected in 11% of patients. The presence of MYC-R was associated with significantly reduced survival, particularly within the initial 24 months following diagnosis.
Adverse prognostic implications were largely apparent in patients with accompanying rearrangement of BCL2 and/or BCL6 translocations (MYC–double-hit/MYC–triple hit status) and an immunoglobulin (IG) partner (hazard ratio, 2.4; 95% confidence interval, 1.6-3.6; P less than .001).
“These data suggest that little justification exists for altering initial therapeutic approaches in patients with DLBCL whose tumors carry an MYC translocation alone [MYC single hit],” they wrote. “However, for [MYC double hit/MYC triple hit] DLBCL, the major negative prognostic impact and 2-year effect support the practice of optimizing first-line treatment approaches to achieve maximum complete response rates because salvage treatment at relapse is not effective.”
Dr. Rosenwald and colleagues suggested that, in the future, diagnostic approaches should be implemented to detect patients in this high-risk group and that risk-modified treatment strategies should be further developed.
The study was supported by unrestricted grants to the Lunenburg Lymphoma Biomarker Consortium from several pharmaceutical companies and Bloodwise. Dr. Rosenwald reported having no conflicts of interest, but several coauthors reported relationships with industry.
SOURCE: : Rosenwald A et al. J Clin Oncol. 2019 Sep 9. doi: 10.1200/JCO.19.00743.
MYC rearrangement (MYC-R) has negative prognostic significance in patients with diffuse large B-cell lymphoma (DLBCL) in relation to the MYC partner gene, according to a retrospective study.
The negative prognostic effect of MYC-R was largely limited to patients with MYC–double hit/MYC–triple hit status and an immunoglobulin (IG) partner within 24 months following diagnosis.
“The primary objective of the study was to validate the prognostic relevance of [MYC–single hit] and [MYC–double hit/MYC–triple hit] status within the context of the MYC translocation partner (MYC-IG v. MYC-non-IG) in patients with DLBCL morphology,” wrote Andreas Rosenwald, MD, of the University of Würzburg (Germany) and colleagues in the Journal of Clinical Oncology.
The researchers identified 5,117 patients who all received R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-CHOP–like immunochemotherapy, 2,383 of whom were evaluable for MYC-R and had complete clinical data. The cohort consisted of patients enrolled in various population-based registries and prospective clinical studies throughout North America and Europe.
The team used fluorescence in situ hybridization testing to identify MYC-R, in addition to BCL2 and/or BCL6 translocations if MYC-R was detected. Subsequently, these data were correlated with clinical endpoints.
After analysis, the researchers found that MYC-R was detected in 11% of patients. The presence of MYC-R was associated with significantly reduced survival, particularly within the initial 24 months following diagnosis.
Adverse prognostic implications were largely apparent in patients with accompanying rearrangement of BCL2 and/or BCL6 translocations (MYC–double-hit/MYC–triple hit status) and an immunoglobulin (IG) partner (hazard ratio, 2.4; 95% confidence interval, 1.6-3.6; P less than .001).
“These data suggest that little justification exists for altering initial therapeutic approaches in patients with DLBCL whose tumors carry an MYC translocation alone [MYC single hit],” they wrote. “However, for [MYC double hit/MYC triple hit] DLBCL, the major negative prognostic impact and 2-year effect support the practice of optimizing first-line treatment approaches to achieve maximum complete response rates because salvage treatment at relapse is not effective.”
Dr. Rosenwald and colleagues suggested that, in the future, diagnostic approaches should be implemented to detect patients in this high-risk group and that risk-modified treatment strategies should be further developed.
The study was supported by unrestricted grants to the Lunenburg Lymphoma Biomarker Consortium from several pharmaceutical companies and Bloodwise. Dr. Rosenwald reported having no conflicts of interest, but several coauthors reported relationships with industry.
SOURCE: : Rosenwald A et al. J Clin Oncol. 2019 Sep 9. doi: 10.1200/JCO.19.00743.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Rituximab, bendamustine look better than chemo alone in MCL
In older patients with newly diagnosed mantle cell lymphoma (MCL), first-line therapy with rituximab- and bendamustine-based regimens significantly reduced 1-year mortality rates versus chemotherapy alone, according to a retrospective analysis.
“This study evaluated the comparative effectiveness of [rituximab, bortezomib, or bendamustine] in elderly patients newly diagnosed with MCL,” wrote Shuangshuang Fu, PhD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues. The findings were reported in Clinical Lymphoma, Myeloma & Leukemia.
The researchers studied population-based data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. They identified all patients over age 65 years who received a new diagnosis of MCL between Jan. 1, 1999, and Dec. 31, 2013.
The study cohort included a total of 1,215 patients. Participants were classified into four different groups according to treatment regimen: chemotherapy alone, rituximab plus or minus chemotherapy, bendamustine plus or minus chemotherapy, and bortezomib plus or minus chemotherapy.
At 1-year follow-up, the team analyzed various mortality outcomes, including MCL-specific, all-cause, and noncancer mortality. The bortezomib results were not included in the primary analysis because of small sample size, according to the researchers.
After multivariable analysis, Dr. Fu and colleagues found that 1-year all-cause mortality rate was significantly lower for patients receiving rituximab-based regimens, compared with chemotherapy alone (hazard ratio, 0.38; 95% confidence interval, 0.25-0.59). There was a similar decline for MCL-specific mortality (HR, 0.38; 95% CI, 0.24-0.60).
The 1-year MCL-specific mortality was also significantly reduced in the bendamustine group, compared with chemotherapy alone (HR, 0.49; 95% CI, 0.24-0.99).
“Our findings comparing rituximab with chemotherapy alone further confirmed the benefit of adding rituximab to chemotherapy in newly diagnosed older MCL patients,” they wrote.
The researchers acknowledged that a key limitation of the study was the observational design. As a result, selection bias and unmeasured confounding could have influenced the results.
“Future studies evaluating the comparative effectiveness of those newly approved novel agents for MCL patients were warranted as more data are available,” they concluded.
The study was funded by the Duncan Family Institute, the Cancer Prevention Research Institute of Texas, and the National Institutes of Health. The authors reported having no conflicts of interest.
SOURCE: Fu S et al. Clin Lymphoma Myeloma Leuk. 2019 Aug 30. doi: 10.1016/j.clml.2019.08.014.
In older patients with newly diagnosed mantle cell lymphoma (MCL), first-line therapy with rituximab- and bendamustine-based regimens significantly reduced 1-year mortality rates versus chemotherapy alone, according to a retrospective analysis.
“This study evaluated the comparative effectiveness of [rituximab, bortezomib, or bendamustine] in elderly patients newly diagnosed with MCL,” wrote Shuangshuang Fu, PhD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues. The findings were reported in Clinical Lymphoma, Myeloma & Leukemia.
The researchers studied population-based data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. They identified all patients over age 65 years who received a new diagnosis of MCL between Jan. 1, 1999, and Dec. 31, 2013.
The study cohort included a total of 1,215 patients. Participants were classified into four different groups according to treatment regimen: chemotherapy alone, rituximab plus or minus chemotherapy, bendamustine plus or minus chemotherapy, and bortezomib plus or minus chemotherapy.
At 1-year follow-up, the team analyzed various mortality outcomes, including MCL-specific, all-cause, and noncancer mortality. The bortezomib results were not included in the primary analysis because of small sample size, according to the researchers.
After multivariable analysis, Dr. Fu and colleagues found that 1-year all-cause mortality rate was significantly lower for patients receiving rituximab-based regimens, compared with chemotherapy alone (hazard ratio, 0.38; 95% confidence interval, 0.25-0.59). There was a similar decline for MCL-specific mortality (HR, 0.38; 95% CI, 0.24-0.60).
The 1-year MCL-specific mortality was also significantly reduced in the bendamustine group, compared with chemotherapy alone (HR, 0.49; 95% CI, 0.24-0.99).
“Our findings comparing rituximab with chemotherapy alone further confirmed the benefit of adding rituximab to chemotherapy in newly diagnosed older MCL patients,” they wrote.
The researchers acknowledged that a key limitation of the study was the observational design. As a result, selection bias and unmeasured confounding could have influenced the results.
“Future studies evaluating the comparative effectiveness of those newly approved novel agents for MCL patients were warranted as more data are available,” they concluded.
The study was funded by the Duncan Family Institute, the Cancer Prevention Research Institute of Texas, and the National Institutes of Health. The authors reported having no conflicts of interest.
SOURCE: Fu S et al. Clin Lymphoma Myeloma Leuk. 2019 Aug 30. doi: 10.1016/j.clml.2019.08.014.
In older patients with newly diagnosed mantle cell lymphoma (MCL), first-line therapy with rituximab- and bendamustine-based regimens significantly reduced 1-year mortality rates versus chemotherapy alone, according to a retrospective analysis.
“This study evaluated the comparative effectiveness of [rituximab, bortezomib, or bendamustine] in elderly patients newly diagnosed with MCL,” wrote Shuangshuang Fu, PhD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues. The findings were reported in Clinical Lymphoma, Myeloma & Leukemia.
The researchers studied population-based data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. They identified all patients over age 65 years who received a new diagnosis of MCL between Jan. 1, 1999, and Dec. 31, 2013.
The study cohort included a total of 1,215 patients. Participants were classified into four different groups according to treatment regimen: chemotherapy alone, rituximab plus or minus chemotherapy, bendamustine plus or minus chemotherapy, and bortezomib plus or minus chemotherapy.
At 1-year follow-up, the team analyzed various mortality outcomes, including MCL-specific, all-cause, and noncancer mortality. The bortezomib results were not included in the primary analysis because of small sample size, according to the researchers.
After multivariable analysis, Dr. Fu and colleagues found that 1-year all-cause mortality rate was significantly lower for patients receiving rituximab-based regimens, compared with chemotherapy alone (hazard ratio, 0.38; 95% confidence interval, 0.25-0.59). There was a similar decline for MCL-specific mortality (HR, 0.38; 95% CI, 0.24-0.60).
The 1-year MCL-specific mortality was also significantly reduced in the bendamustine group, compared with chemotherapy alone (HR, 0.49; 95% CI, 0.24-0.99).
“Our findings comparing rituximab with chemotherapy alone further confirmed the benefit of adding rituximab to chemotherapy in newly diagnosed older MCL patients,” they wrote.
The researchers acknowledged that a key limitation of the study was the observational design. As a result, selection bias and unmeasured confounding could have influenced the results.
“Future studies evaluating the comparative effectiveness of those newly approved novel agents for MCL patients were warranted as more data are available,” they concluded.
The study was funded by the Duncan Family Institute, the Cancer Prevention Research Institute of Texas, and the National Institutes of Health. The authors reported having no conflicts of interest.
SOURCE: Fu S et al. Clin Lymphoma Myeloma Leuk. 2019 Aug 30. doi: 10.1016/j.clml.2019.08.014.
FROM CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA
CK doesn’t seem to affect OS in CLL patients taking idelalisib
The presence of complex karyotype (CK) does not affect survival in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who are treated with idelalisib, according to a new analysis.
Researchers analyzed data from two clinical trials of idelalisib, given alone or in combination with rituximab, and found no significant difference in overall survival (OS) between patients with and without CK.
Karl-Anton Kreuzer, MD, of the University of Cologne (Germany), and colleagues described these findings in a letter to Leukemia.
The researchers evaluated patients with previously treated CLL who were enrolled in a phase 3 trial and received either idelalisib plus rituximab or rituximab plus placebo. Patients from either treatment arm could enroll in an extension study of idelalisib monotherapy.
There were 220 patients randomized to idelalisib plus rituximab (n = 110) or placebo plus rituximab (n = 110) in the primary study, and 161 of these patients were enrolled in the extension study.
The final analysis included 120 patients who were successfully karyotyped – 63 from the idelalisib-rituximab arm and 57 from the placebo-rituximab arm. Less than half of patients in each arm were CK-positive – 41% (26/63) of the idelalisib arm and 42% (24/57) of the placebo arm.
The researchers wrote that baseline characteristics were “mostly balanced” between the CK-positive and CK-negative groups in each treatment arm. The only significant difference was that fewer CK-positive patients in the placebo arm had a creatinine clearance of 30-59 mL/min (P = .0324).
Results
There were no significant differences in outcomes between CK-positive and CK-negative patients who received idelalisib and rituximab. The overall response rate was 81% in CK-positive patients and 89% in CK-negative patients (P = .3509). The median progression-free survival was 20.9 months and 19.4 months, respectively (P = .5848).
The median OS was 28.3 months in the CK-positive group and 49.7 months in the CK-negative group (P = .2099). The copresence of CK and del(17p), TP53 mutation, or del(11q) didn’t significantly affect OS, the researchers noted.
Among all CK-positive patients, the median OS was 28.3 months in the idelalisib-rituximab arm and 9.2 months in the placebo-rituximab arm (P = .0412).
“Our analysis suggests that CK-positive patients treated with idelalisib/rituximab did not exhibit a significantly shortened survival compared with those who were CK negative,” the researchers wrote. “In addition, the primary beneficial effect of adding idelalisib to rituximab treatment in [relapsed/refractory] CLL patients with CK was reflected in OS prolongation compared to those who received only rituximab.”
The researchers noted that this study has limitations, so prospective clinical trials are needed to guide treatment of patients with relapsed/refractory CLL and CK.
Both trials of idelalisib were sponsored by Gilead. The researchers reported relationships, including employment, with Gilead and other companies. They also disclosed funding from the German government and from nonprofit organizations in Germany.
SOURCE: Kreuzer K-A et al. Leukemia. 2019 Aug 19. doi: 10.1038/s41375-019-0533-6.
The presence of complex karyotype (CK) does not affect survival in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who are treated with idelalisib, according to a new analysis.
Researchers analyzed data from two clinical trials of idelalisib, given alone or in combination with rituximab, and found no significant difference in overall survival (OS) between patients with and without CK.
Karl-Anton Kreuzer, MD, of the University of Cologne (Germany), and colleagues described these findings in a letter to Leukemia.
The researchers evaluated patients with previously treated CLL who were enrolled in a phase 3 trial and received either idelalisib plus rituximab or rituximab plus placebo. Patients from either treatment arm could enroll in an extension study of idelalisib monotherapy.
There were 220 patients randomized to idelalisib plus rituximab (n = 110) or placebo plus rituximab (n = 110) in the primary study, and 161 of these patients were enrolled in the extension study.
The final analysis included 120 patients who were successfully karyotyped – 63 from the idelalisib-rituximab arm and 57 from the placebo-rituximab arm. Less than half of patients in each arm were CK-positive – 41% (26/63) of the idelalisib arm and 42% (24/57) of the placebo arm.
The researchers wrote that baseline characteristics were “mostly balanced” between the CK-positive and CK-negative groups in each treatment arm. The only significant difference was that fewer CK-positive patients in the placebo arm had a creatinine clearance of 30-59 mL/min (P = .0324).
Results
There were no significant differences in outcomes between CK-positive and CK-negative patients who received idelalisib and rituximab. The overall response rate was 81% in CK-positive patients and 89% in CK-negative patients (P = .3509). The median progression-free survival was 20.9 months and 19.4 months, respectively (P = .5848).
The median OS was 28.3 months in the CK-positive group and 49.7 months in the CK-negative group (P = .2099). The copresence of CK and del(17p), TP53 mutation, or del(11q) didn’t significantly affect OS, the researchers noted.
Among all CK-positive patients, the median OS was 28.3 months in the idelalisib-rituximab arm and 9.2 months in the placebo-rituximab arm (P = .0412).
“Our analysis suggests that CK-positive patients treated with idelalisib/rituximab did not exhibit a significantly shortened survival compared with those who were CK negative,” the researchers wrote. “In addition, the primary beneficial effect of adding idelalisib to rituximab treatment in [relapsed/refractory] CLL patients with CK was reflected in OS prolongation compared to those who received only rituximab.”
The researchers noted that this study has limitations, so prospective clinical trials are needed to guide treatment of patients with relapsed/refractory CLL and CK.
Both trials of idelalisib were sponsored by Gilead. The researchers reported relationships, including employment, with Gilead and other companies. They also disclosed funding from the German government and from nonprofit organizations in Germany.
SOURCE: Kreuzer K-A et al. Leukemia. 2019 Aug 19. doi: 10.1038/s41375-019-0533-6.
The presence of complex karyotype (CK) does not affect survival in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who are treated with idelalisib, according to a new analysis.
Researchers analyzed data from two clinical trials of idelalisib, given alone or in combination with rituximab, and found no significant difference in overall survival (OS) between patients with and without CK.
Karl-Anton Kreuzer, MD, of the University of Cologne (Germany), and colleagues described these findings in a letter to Leukemia.
The researchers evaluated patients with previously treated CLL who were enrolled in a phase 3 trial and received either idelalisib plus rituximab or rituximab plus placebo. Patients from either treatment arm could enroll in an extension study of idelalisib monotherapy.
There were 220 patients randomized to idelalisib plus rituximab (n = 110) or placebo plus rituximab (n = 110) in the primary study, and 161 of these patients were enrolled in the extension study.
The final analysis included 120 patients who were successfully karyotyped – 63 from the idelalisib-rituximab arm and 57 from the placebo-rituximab arm. Less than half of patients in each arm were CK-positive – 41% (26/63) of the idelalisib arm and 42% (24/57) of the placebo arm.
The researchers wrote that baseline characteristics were “mostly balanced” between the CK-positive and CK-negative groups in each treatment arm. The only significant difference was that fewer CK-positive patients in the placebo arm had a creatinine clearance of 30-59 mL/min (P = .0324).
Results
There were no significant differences in outcomes between CK-positive and CK-negative patients who received idelalisib and rituximab. The overall response rate was 81% in CK-positive patients and 89% in CK-negative patients (P = .3509). The median progression-free survival was 20.9 months and 19.4 months, respectively (P = .5848).
The median OS was 28.3 months in the CK-positive group and 49.7 months in the CK-negative group (P = .2099). The copresence of CK and del(17p), TP53 mutation, or del(11q) didn’t significantly affect OS, the researchers noted.
Among all CK-positive patients, the median OS was 28.3 months in the idelalisib-rituximab arm and 9.2 months in the placebo-rituximab arm (P = .0412).
“Our analysis suggests that CK-positive patients treated with idelalisib/rituximab did not exhibit a significantly shortened survival compared with those who were CK negative,” the researchers wrote. “In addition, the primary beneficial effect of adding idelalisib to rituximab treatment in [relapsed/refractory] CLL patients with CK was reflected in OS prolongation compared to those who received only rituximab.”
The researchers noted that this study has limitations, so prospective clinical trials are needed to guide treatment of patients with relapsed/refractory CLL and CK.
Both trials of idelalisib were sponsored by Gilead. The researchers reported relationships, including employment, with Gilead and other companies. They also disclosed funding from the German government and from nonprofit organizations in Germany.
SOURCE: Kreuzer K-A et al. Leukemia. 2019 Aug 19. doi: 10.1038/s41375-019-0533-6.
FROM LEUKEMIA
Ibrutinib-rituximab induction yields ‘unprecedented’ responses in MCL
LUGANO, Switzerland – In younger patients with previously untreated mantle cell lymphoma, the chemotherapy-free combination of ibrutinib and rituximab followed by a short course of chemotherapy was associated with an “unprecedented” 3-year progression-free survival rate, investigators in the phase 2 WINDOW-1 trial reported.
Among 50 patients aged 65 years and younger who received ibrutinib and rituximab until they achieved a complete or partial response, followed by four cycles of chemotherapy with rituximab plus hyper-CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone) and rituximab plus methotrexate, the 3-year progression-free survival (PFS) rate was 88%, said Michael Wang, MD, from the University of Texas MD Anderson Cancer Center in Houston.
Additionally, for patients with the low-risk features, the 3-year PFS rate was 90%.
“Chemo-free ibrutinib-rituximab induced unprecedented – unprecedented – efficacy before chemo consolidation,” he said at the International Conference on Malignant Lymphoma.
Dr. Wang presented data from an interim analysis of the investigator-initiated single-center trial. Fifty patients aged 65 years or younger with untreated mantle cell lymphoma (MCL), good performance status, and good organ function were enrolled.
The patients were treated with ibrutinib and rituximab for two cycles and then evaluated for response with PET-CT scan, bone marrow biopsy, and for some patients, esophagogastroduodenoscopy (EGD) and colonoscopy with random biopsies.
In the induction phase, patients received ibrutinib daily on days 1-28 and rituximab intravenously over 6-8 hours on days 1, 8, 15, and 22 of cycle 1, and then over 4 hours on day 1 of cycles 3-12. The treatment was repeated every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity, or until patients achieved a complete response.
In the consolidation phase, patients received rituximab IV over 6 hours on day 1; oral or IV dexamethasone on days 1-4; cyclophosphamide IV over 3 hours twice daily on days 2-4; doxorubicin IV over 15-30 minutes on day 5; and vincristine IV over 15-30 minutes on day 5 of cycles one, three, five, and seven. Patients also received rituximab IV over 6 hours on day 1; methotrexate IV over 24 hours on day 2; and cytarabine IV over 2 hours twice daily on days 3 and 4 of cycles two, four, six, and eight. Treatments were repeated every 28 days for up to eight cycles in the absence of disease progression or unacceptable toxicity.
Patients who had a complete response (CR) after two cycles of induction and those who had disease progression on induction went on to consolidation. Patients with partial responses (PR) to induction continued on ibrutinib/rituximab until either the loss of a PR or best response for up to 12 cycles, with those who achieved a CR then moving on to consolidation.
Patients who had a CR after induction received four cycles of R-hyperCVAD, no subsequent stem cell transplant, and no maintenance therapy. Patients who had a PR after induction received two cycles of R-hyperCVAD, were reassessed, and then continued on R-hyperCVAD until CR or for up to eight total cycles.
Patients with either stable disease or progression during R-hyperCVAD were taken off the study.
Of the 50 patients enrolled, all 50 were evaluable for part A (induction), and 48 were evaluable after induction and consolidation (two patients withdrew for personal reasons).
After a median follow-up of 36 months, the overall response rate (ORR) following induction was 100%, consisting of 46 CRs (92%) and four PRs (8%).
In an intention-to-treat analysis (including the two patients who withdrew), the ORR was 96%, consisting of CRs in 47 patients (94%) and a PR in 1 patient (2%).
Neither the median PFS nor median overall survival had been reached at the time of data cutoff, and no patients have died.
Of the 50 enrolled patients, four experienced disease progression after 17, 24, 34, and 35 months of treatment. The patients with disease progression included one with Ki-67 of less than 30%, and three with KI-67 of 30% or greater.
Grade 3-4 toxicities during induction including myelosuppression in 4%; fatigue, myalgia, and rashes in 8% each; and oral mucositis in 4%.
Dr. Wang said that future studies on minimal residual disease and clonal evolution are ongoing, and that data on more patients will be presented at the next annual meeting of the American Society of Hematology, scheduled for December 2019.
He also noted that the WINDOW-2 trial, in which ibrutinib and rituximab are followed by veneotclax and hyper-CVAD chemotherapy in patients with newly diagnosed MCL, is open and rapidly enrolling patients.
The study is supported by the National Cancer Institute. Dr. Wang reported financial relationships with Janssen, Pharmacyclics, and other companies.
SOURCE: Wang M et al. ICML-15, Abstract 12.
LUGANO, Switzerland – In younger patients with previously untreated mantle cell lymphoma, the chemotherapy-free combination of ibrutinib and rituximab followed by a short course of chemotherapy was associated with an “unprecedented” 3-year progression-free survival rate, investigators in the phase 2 WINDOW-1 trial reported.
Among 50 patients aged 65 years and younger who received ibrutinib and rituximab until they achieved a complete or partial response, followed by four cycles of chemotherapy with rituximab plus hyper-CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone) and rituximab plus methotrexate, the 3-year progression-free survival (PFS) rate was 88%, said Michael Wang, MD, from the University of Texas MD Anderson Cancer Center in Houston.
Additionally, for patients with the low-risk features, the 3-year PFS rate was 90%.
“Chemo-free ibrutinib-rituximab induced unprecedented – unprecedented – efficacy before chemo consolidation,” he said at the International Conference on Malignant Lymphoma.
Dr. Wang presented data from an interim analysis of the investigator-initiated single-center trial. Fifty patients aged 65 years or younger with untreated mantle cell lymphoma (MCL), good performance status, and good organ function were enrolled.
The patients were treated with ibrutinib and rituximab for two cycles and then evaluated for response with PET-CT scan, bone marrow biopsy, and for some patients, esophagogastroduodenoscopy (EGD) and colonoscopy with random biopsies.
In the induction phase, patients received ibrutinib daily on days 1-28 and rituximab intravenously over 6-8 hours on days 1, 8, 15, and 22 of cycle 1, and then over 4 hours on day 1 of cycles 3-12. The treatment was repeated every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity, or until patients achieved a complete response.
In the consolidation phase, patients received rituximab IV over 6 hours on day 1; oral or IV dexamethasone on days 1-4; cyclophosphamide IV over 3 hours twice daily on days 2-4; doxorubicin IV over 15-30 minutes on day 5; and vincristine IV over 15-30 minutes on day 5 of cycles one, three, five, and seven. Patients also received rituximab IV over 6 hours on day 1; methotrexate IV over 24 hours on day 2; and cytarabine IV over 2 hours twice daily on days 3 and 4 of cycles two, four, six, and eight. Treatments were repeated every 28 days for up to eight cycles in the absence of disease progression or unacceptable toxicity.
Patients who had a complete response (CR) after two cycles of induction and those who had disease progression on induction went on to consolidation. Patients with partial responses (PR) to induction continued on ibrutinib/rituximab until either the loss of a PR or best response for up to 12 cycles, with those who achieved a CR then moving on to consolidation.
Patients who had a CR after induction received four cycles of R-hyperCVAD, no subsequent stem cell transplant, and no maintenance therapy. Patients who had a PR after induction received two cycles of R-hyperCVAD, were reassessed, and then continued on R-hyperCVAD until CR or for up to eight total cycles.
Patients with either stable disease or progression during R-hyperCVAD were taken off the study.
Of the 50 patients enrolled, all 50 were evaluable for part A (induction), and 48 were evaluable after induction and consolidation (two patients withdrew for personal reasons).
After a median follow-up of 36 months, the overall response rate (ORR) following induction was 100%, consisting of 46 CRs (92%) and four PRs (8%).
In an intention-to-treat analysis (including the two patients who withdrew), the ORR was 96%, consisting of CRs in 47 patients (94%) and a PR in 1 patient (2%).
Neither the median PFS nor median overall survival had been reached at the time of data cutoff, and no patients have died.
Of the 50 enrolled patients, four experienced disease progression after 17, 24, 34, and 35 months of treatment. The patients with disease progression included one with Ki-67 of less than 30%, and three with KI-67 of 30% or greater.
Grade 3-4 toxicities during induction including myelosuppression in 4%; fatigue, myalgia, and rashes in 8% each; and oral mucositis in 4%.
Dr. Wang said that future studies on minimal residual disease and clonal evolution are ongoing, and that data on more patients will be presented at the next annual meeting of the American Society of Hematology, scheduled for December 2019.
He also noted that the WINDOW-2 trial, in which ibrutinib and rituximab are followed by veneotclax and hyper-CVAD chemotherapy in patients with newly diagnosed MCL, is open and rapidly enrolling patients.
The study is supported by the National Cancer Institute. Dr. Wang reported financial relationships with Janssen, Pharmacyclics, and other companies.
SOURCE: Wang M et al. ICML-15, Abstract 12.
LUGANO, Switzerland – In younger patients with previously untreated mantle cell lymphoma, the chemotherapy-free combination of ibrutinib and rituximab followed by a short course of chemotherapy was associated with an “unprecedented” 3-year progression-free survival rate, investigators in the phase 2 WINDOW-1 trial reported.
Among 50 patients aged 65 years and younger who received ibrutinib and rituximab until they achieved a complete or partial response, followed by four cycles of chemotherapy with rituximab plus hyper-CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone) and rituximab plus methotrexate, the 3-year progression-free survival (PFS) rate was 88%, said Michael Wang, MD, from the University of Texas MD Anderson Cancer Center in Houston.
Additionally, for patients with the low-risk features, the 3-year PFS rate was 90%.
“Chemo-free ibrutinib-rituximab induced unprecedented – unprecedented – efficacy before chemo consolidation,” he said at the International Conference on Malignant Lymphoma.
Dr. Wang presented data from an interim analysis of the investigator-initiated single-center trial. Fifty patients aged 65 years or younger with untreated mantle cell lymphoma (MCL), good performance status, and good organ function were enrolled.
The patients were treated with ibrutinib and rituximab for two cycles and then evaluated for response with PET-CT scan, bone marrow biopsy, and for some patients, esophagogastroduodenoscopy (EGD) and colonoscopy with random biopsies.
In the induction phase, patients received ibrutinib daily on days 1-28 and rituximab intravenously over 6-8 hours on days 1, 8, 15, and 22 of cycle 1, and then over 4 hours on day 1 of cycles 3-12. The treatment was repeated every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity, or until patients achieved a complete response.
In the consolidation phase, patients received rituximab IV over 6 hours on day 1; oral or IV dexamethasone on days 1-4; cyclophosphamide IV over 3 hours twice daily on days 2-4; doxorubicin IV over 15-30 minutes on day 5; and vincristine IV over 15-30 minutes on day 5 of cycles one, three, five, and seven. Patients also received rituximab IV over 6 hours on day 1; methotrexate IV over 24 hours on day 2; and cytarabine IV over 2 hours twice daily on days 3 and 4 of cycles two, four, six, and eight. Treatments were repeated every 28 days for up to eight cycles in the absence of disease progression or unacceptable toxicity.
Patients who had a complete response (CR) after two cycles of induction and those who had disease progression on induction went on to consolidation. Patients with partial responses (PR) to induction continued on ibrutinib/rituximab until either the loss of a PR or best response for up to 12 cycles, with those who achieved a CR then moving on to consolidation.
Patients who had a CR after induction received four cycles of R-hyperCVAD, no subsequent stem cell transplant, and no maintenance therapy. Patients who had a PR after induction received two cycles of R-hyperCVAD, were reassessed, and then continued on R-hyperCVAD until CR or for up to eight total cycles.
Patients with either stable disease or progression during R-hyperCVAD were taken off the study.
Of the 50 patients enrolled, all 50 were evaluable for part A (induction), and 48 were evaluable after induction and consolidation (two patients withdrew for personal reasons).
After a median follow-up of 36 months, the overall response rate (ORR) following induction was 100%, consisting of 46 CRs (92%) and four PRs (8%).
In an intention-to-treat analysis (including the two patients who withdrew), the ORR was 96%, consisting of CRs in 47 patients (94%) and a PR in 1 patient (2%).
Neither the median PFS nor median overall survival had been reached at the time of data cutoff, and no patients have died.
Of the 50 enrolled patients, four experienced disease progression after 17, 24, 34, and 35 months of treatment. The patients with disease progression included one with Ki-67 of less than 30%, and three with KI-67 of 30% or greater.
Grade 3-4 toxicities during induction including myelosuppression in 4%; fatigue, myalgia, and rashes in 8% each; and oral mucositis in 4%.
Dr. Wang said that future studies on minimal residual disease and clonal evolution are ongoing, and that data on more patients will be presented at the next annual meeting of the American Society of Hematology, scheduled for December 2019.
He also noted that the WINDOW-2 trial, in which ibrutinib and rituximab are followed by veneotclax and hyper-CVAD chemotherapy in patients with newly diagnosed MCL, is open and rapidly enrolling patients.
The study is supported by the National Cancer Institute. Dr. Wang reported financial relationships with Janssen, Pharmacyclics, and other companies.
SOURCE: Wang M et al. ICML-15, Abstract 12.
REPORTING FROM 15-ICML
Calquence earns breakthrough designation for CLL monotherapy
The Bruton tyrosine kinase inhibitor is already approved for the treatment of adults with mantle cell lymphoma who have received at least one prior therapy, and multiple trials are underway to evaluate the drug’s use in a variety of B-cell malignancies, according to the drug’s sponsor, AstraZeneca.
The current designation was based on preliminary results from two phase 3 trials – ELEVATE-TN and ASCEND. In the three-arm ELEVATE-TN trial, researchers evaluated acalabrutinib alone or in combination with obinutuzumab versus chlorambucil plus obinutuzumab in previously untreated patients with CLL. In the two-arm ASCEND trial, previously treated patients with CLL were randomized to receive acalabrutinib monotherapy or the physician’s choice of either rituximab plus idelalisib or rituximab plus bendamustine.
Interim analyses of the two trials showed that acalabrutinib alone, or in combination, significantly improved progression-free survival without raising safety concerns.
Breakthrough therapy designation allows for an expedited review by the FDA for treatments aimed at treating serious conditions where there is preliminary clinical evidence showing a substantial improvement over an available therapy or a clinically significant endpoint.
The Bruton tyrosine kinase inhibitor is already approved for the treatment of adults with mantle cell lymphoma who have received at least one prior therapy, and multiple trials are underway to evaluate the drug’s use in a variety of B-cell malignancies, according to the drug’s sponsor, AstraZeneca.
The current designation was based on preliminary results from two phase 3 trials – ELEVATE-TN and ASCEND. In the three-arm ELEVATE-TN trial, researchers evaluated acalabrutinib alone or in combination with obinutuzumab versus chlorambucil plus obinutuzumab in previously untreated patients with CLL. In the two-arm ASCEND trial, previously treated patients with CLL were randomized to receive acalabrutinib monotherapy or the physician’s choice of either rituximab plus idelalisib or rituximab plus bendamustine.
Interim analyses of the two trials showed that acalabrutinib alone, or in combination, significantly improved progression-free survival without raising safety concerns.
Breakthrough therapy designation allows for an expedited review by the FDA for treatments aimed at treating serious conditions where there is preliminary clinical evidence showing a substantial improvement over an available therapy or a clinically significant endpoint.
The Bruton tyrosine kinase inhibitor is already approved for the treatment of adults with mantle cell lymphoma who have received at least one prior therapy, and multiple trials are underway to evaluate the drug’s use in a variety of B-cell malignancies, according to the drug’s sponsor, AstraZeneca.
The current designation was based on preliminary results from two phase 3 trials – ELEVATE-TN and ASCEND. In the three-arm ELEVATE-TN trial, researchers evaluated acalabrutinib alone or in combination with obinutuzumab versus chlorambucil plus obinutuzumab in previously untreated patients with CLL. In the two-arm ASCEND trial, previously treated patients with CLL were randomized to receive acalabrutinib monotherapy or the physician’s choice of either rituximab plus idelalisib or rituximab plus bendamustine.
Interim analyses of the two trials showed that acalabrutinib alone, or in combination, significantly improved progression-free survival without raising safety concerns.
Breakthrough therapy designation allows for an expedited review by the FDA for treatments aimed at treating serious conditions where there is preliminary clinical evidence showing a substantial improvement over an available therapy or a clinically significant endpoint.
Obinutuzumab-lenalidomide combo shows promise in relapsed/refractory FL
Obinutuzumab plus lenalidomide showed manageable safety and activity in patients with relapsed/refractory follicular lymphoma (FL), according to results from a phase 2 trial.
“The results of this phase 2 study show that induction therapy with obinutuzumab and lenalidomide followed by maintenance therapy with obinutuzumab is effective for many patients with relapsed or refractory follicular lymphoma,” wrote Franck Morschhauser, MD, PhD, of the University of Lille, France, and colleagues. The results were published in The Lancet Haematology.
The multicenter, single-arm study comprised 89 patients, 88 of whom were assessed for safety and 86 for efficacy. All eligible study patients received a minimum of one prior rituximab-based therapy before receiving obinutuzumab.
Study participants received intravenous obinutuzumab 1,000 mg for six 28-day cycles, in addition to oral lenalidomide 20 mg as induction therapy.
Maintenance therapy (year 1) consisted of oral lenalidomide 10 mg on days 2-22 of each cycle for a maximum of 12 28-day cycles plus obinutuzumab 1,000 mg on day 1 of alternate cycles (total of six infusions). Maintenance therapy (year 2) consisted of obinutuzumab 1,000 mg alone on day 1 for six 56-day cycles.
The primary outcome was the proportion of patients who achieved an overall response at the end of induction therapy. Secondary outcomes included various survival parameters and safety.
After analysis, the researchers found that the proportion of patients who achieved an overall response at induction end was 79% (95% confidence interval, 69-87). In addition, 38% of patients (95% CI, 28-50) had achieved a complete response at the end of induction therapy.
The progression-free survival, event-free survival, and overall survival rates were 65% (95% CI, 54-74), 62% (95% CI, 51-72), and 87% (95% CI, 78-93), respectively, at 2 years (no P values were reported).
“The results suggest that obinutuzumab plus lenalidomide is active as shown by 2-year outcomes (progression-free survival and overall survival) in the overall patient group,” the researchers wrote.
With respect to safety, basal cell carcinoma (6%), febrile neutropenia (5%), and infusion-related reactions (3%) were the most frequently reported serious toxicities. One patient died because of therapy-related febrile neutropenia.
The Lymphoma Academic Research Organisation, Celgene, and Roche funded the study. The authors reported financial affiliations with the study sponsors and several other companies.
SOURCE: Morschhauser F et al. Lancet Haematol. 2019 Jul 8. doi: 10.1016/S2352-3026(19)30089-4.
Obinutuzumab plus lenalidomide showed manageable safety and activity in patients with relapsed/refractory follicular lymphoma (FL), according to results from a phase 2 trial.
“The results of this phase 2 study show that induction therapy with obinutuzumab and lenalidomide followed by maintenance therapy with obinutuzumab is effective for many patients with relapsed or refractory follicular lymphoma,” wrote Franck Morschhauser, MD, PhD, of the University of Lille, France, and colleagues. The results were published in The Lancet Haematology.
The multicenter, single-arm study comprised 89 patients, 88 of whom were assessed for safety and 86 for efficacy. All eligible study patients received a minimum of one prior rituximab-based therapy before receiving obinutuzumab.
Study participants received intravenous obinutuzumab 1,000 mg for six 28-day cycles, in addition to oral lenalidomide 20 mg as induction therapy.
Maintenance therapy (year 1) consisted of oral lenalidomide 10 mg on days 2-22 of each cycle for a maximum of 12 28-day cycles plus obinutuzumab 1,000 mg on day 1 of alternate cycles (total of six infusions). Maintenance therapy (year 2) consisted of obinutuzumab 1,000 mg alone on day 1 for six 56-day cycles.
The primary outcome was the proportion of patients who achieved an overall response at the end of induction therapy. Secondary outcomes included various survival parameters and safety.
After analysis, the researchers found that the proportion of patients who achieved an overall response at induction end was 79% (95% confidence interval, 69-87). In addition, 38% of patients (95% CI, 28-50) had achieved a complete response at the end of induction therapy.
The progression-free survival, event-free survival, and overall survival rates were 65% (95% CI, 54-74), 62% (95% CI, 51-72), and 87% (95% CI, 78-93), respectively, at 2 years (no P values were reported).
“The results suggest that obinutuzumab plus lenalidomide is active as shown by 2-year outcomes (progression-free survival and overall survival) in the overall patient group,” the researchers wrote.
With respect to safety, basal cell carcinoma (6%), febrile neutropenia (5%), and infusion-related reactions (3%) were the most frequently reported serious toxicities. One patient died because of therapy-related febrile neutropenia.
The Lymphoma Academic Research Organisation, Celgene, and Roche funded the study. The authors reported financial affiliations with the study sponsors and several other companies.
SOURCE: Morschhauser F et al. Lancet Haematol. 2019 Jul 8. doi: 10.1016/S2352-3026(19)30089-4.
Obinutuzumab plus lenalidomide showed manageable safety and activity in patients with relapsed/refractory follicular lymphoma (FL), according to results from a phase 2 trial.
“The results of this phase 2 study show that induction therapy with obinutuzumab and lenalidomide followed by maintenance therapy with obinutuzumab is effective for many patients with relapsed or refractory follicular lymphoma,” wrote Franck Morschhauser, MD, PhD, of the University of Lille, France, and colleagues. The results were published in The Lancet Haematology.
The multicenter, single-arm study comprised 89 patients, 88 of whom were assessed for safety and 86 for efficacy. All eligible study patients received a minimum of one prior rituximab-based therapy before receiving obinutuzumab.
Study participants received intravenous obinutuzumab 1,000 mg for six 28-day cycles, in addition to oral lenalidomide 20 mg as induction therapy.
Maintenance therapy (year 1) consisted of oral lenalidomide 10 mg on days 2-22 of each cycle for a maximum of 12 28-day cycles plus obinutuzumab 1,000 mg on day 1 of alternate cycles (total of six infusions). Maintenance therapy (year 2) consisted of obinutuzumab 1,000 mg alone on day 1 for six 56-day cycles.
The primary outcome was the proportion of patients who achieved an overall response at the end of induction therapy. Secondary outcomes included various survival parameters and safety.
After analysis, the researchers found that the proportion of patients who achieved an overall response at induction end was 79% (95% confidence interval, 69-87). In addition, 38% of patients (95% CI, 28-50) had achieved a complete response at the end of induction therapy.
The progression-free survival, event-free survival, and overall survival rates were 65% (95% CI, 54-74), 62% (95% CI, 51-72), and 87% (95% CI, 78-93), respectively, at 2 years (no P values were reported).
“The results suggest that obinutuzumab plus lenalidomide is active as shown by 2-year outcomes (progression-free survival and overall survival) in the overall patient group,” the researchers wrote.
With respect to safety, basal cell carcinoma (6%), febrile neutropenia (5%), and infusion-related reactions (3%) were the most frequently reported serious toxicities. One patient died because of therapy-related febrile neutropenia.
The Lymphoma Academic Research Organisation, Celgene, and Roche funded the study. The authors reported financial affiliations with the study sponsors and several other companies.
SOURCE: Morschhauser F et al. Lancet Haematol. 2019 Jul 8. doi: 10.1016/S2352-3026(19)30089-4.
FROM THE LANCET HAEMATOLOGY