B-Cell Lymphoma ICYMI

Key clinical point: Brexucabtagene autoleucel (brexu-cel) demonstrated promising efficacy and a favorable safety profile in patients with relapsed or refractory mantle cell lymphoma (MCL) in real-world practice, which is consistent with that reported in the ZUMA-2 trial.

Major finding: At a median follow-up of 14.3 months after infusion, the best overall and complete response rates were 90% and 82%, respectively. The 6- and 12-month progression-free survival rates were 69% (95% CI 61%-75%) and 59% (95% CI 51%-66%), respectively. The grade ≥3 cytokine release syndrome and neurotoxicity rates were 8% and 32%, respectively.

Study details: This multicenter retrospective study included 189 patients with relapsed or refractory MCL who underwent leukapheresis for commercial manufacturing of brexu-cel, of which 168 received brexu-cel infusion.

Disclosures: This study was sponsored by a US National Cancer Institute cancer support grant. Some authors reported ties with various organizations.

Source: Wang Y et al. Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: Results from the US Lymphoma CAR T Consortium. J Clin Oncol. 2023 (Feb 8). Doi: 10.1200/JCO.22.01797

Key clinical point: Brexucabtagene autoleucel (brexu-cel) demonstrated promising efficacy and a favorable safety profile in patients with relapsed or refractory mantle cell lymphoma (MCL) in real-world practice, which is consistent with that reported in the ZUMA-2 trial.

Major finding: At a median follow-up of 14.3 months after infusion, the best overall and complete response rates were 90% and 82%, respectively. The 6- and 12-month progression-free survival rates were 69% (95% CI 61%-75%) and 59% (95% CI 51%-66%), respectively. The grade ≥3 cytokine release syndrome and neurotoxicity rates were 8% and 32%, respectively.

Study details: This multicenter retrospective study included 189 patients with relapsed or refractory MCL who underwent leukapheresis for commercial manufacturing of brexu-cel, of which 168 received brexu-cel infusion.

Disclosures: This study was sponsored by a US National Cancer Institute cancer support grant. Some authors reported ties with various organizations.

Source: Wang Y et al. Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: Results from the US Lymphoma CAR T Consortium. J Clin Oncol. 2023 (Feb 8). Doi: 10.1200/JCO.22.01797

Key clinical point: Brexucabtagene autoleucel (brexu-cel) demonstrated promising efficacy and a favorable safety profile in patients with relapsed or refractory mantle cell lymphoma (MCL) in real-world practice, which is consistent with that reported in the ZUMA-2 trial.

Major finding: At a median follow-up of 14.3 months after infusion, the best overall and complete response rates were 90% and 82%, respectively. The 6- and 12-month progression-free survival rates were 69% (95% CI 61%-75%) and 59% (95% CI 51%-66%), respectively. The grade ≥3 cytokine release syndrome and neurotoxicity rates were 8% and 32%, respectively.

Study details: This multicenter retrospective study included 189 patients with relapsed or refractory MCL who underwent leukapheresis for commercial manufacturing of brexu-cel, of which 168 received brexu-cel infusion.

Disclosures: This study was sponsored by a US National Cancer Institute cancer support grant. Some authors reported ties with various organizations.

Source: Wang Y et al. Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: Results from the US Lymphoma CAR T Consortium. J Clin Oncol. 2023 (Feb 8). Doi: 10.1200/JCO.22.01797

As various surgical procedures become more feasible for patients with chronic lymphocytic leukemia (CLL), a team of hematologist-oncologists and cardiologists published a new report advising colleagues to carefully consider the risks and benefits of such operations.

In the past decade, as targeted therapies have permitted better management of CLL, a new realm of possibilities has opened up for patients with this blood cancer.

“Previously, patients may not have been candidates for elective surgeries, such as hip replacements,” said hematologist-oncologist Helen Ma, MD, of the University of Irvine (Calif.) and VA Long Beach Healthcare System. She is the lead author of the report, which appeared in the British Journal of Hematology.

“Now that targeted therapies are controlling CLL well, patients may elect to have procedures that they may not have considered if their blood counts were very low or they felt too unwell to go through such invasive surgeries,” said Dr. Ma in an interview. In fact, the study authors noted that, “with currently available treatments, many patients with CLL are living considerably longer than the 1-year life expectancy threshold that proceduralists require.”

But extra surgical risks persist. “Both CLL and its treatment can increase the risk of complications during and after procedures, though available data are not consistently stratified by stage and whether patients are undergoing treatment,” the report authors noted.

Research has linked CLL to higher rates of blood transfusions in cardiac surgeries: One study, conducted partially in the era of targeted therapy, found that 87% of these surgery patients with CLL needed blood products vs. 65% of those who didn’t have CLL (P = .01). Studies didn’t find any extra risk of infections in patients with CLL, however, and there are conflicting findings about whether hospital mortality is higher.

Another study, also conducted partially in the era of targeted therapy, found that patients with CLL who had percutaneous coronary intervention procedures “developed higher rates of in-hospital mortality, any complication, bleeding and postoperative stroke compared to those seen in patients without leukemia.”

The authors of the new report noted that “patients with more advanced stage are at increased risk of bleeding and thromboembolic events relevant to their disease and invasive procedures.” Patients at more than minimal risk should undergo electrocardiograms prior to cardiac procedures, they wrote. Stress tests, coronary angiography, and percutaneous coronary intervention may also be warranted.

“To optimize evaluation and perioperative management, we strongly recommend the prospective collaborative inclusion of a multidisciplinary team including hematologists/oncologists, cardiologists (ideally cardio-oncologists), surgeons and anesthetists, as well as their ongoing involvement during the postoperative period,” the authors wrote.

As for medications, the researchers said that “generally, antibody therapy has no impact on surgery.” They added, “There is no evidence to hold treatment with anti-CD20 monoclonal antibodies prior to procedures unless the patient has cytopenias that may be a contra-indication. If that is the case, we recommend holding until counts recover to the parameters required for the procedure.”

In regard to Bruton’s tyrosine kinase inhibitors such as ibrutinib, “patients undergoing major surgeries with high risk of bleeding should hold Bruton’s tyrosine kinase inhibitors for a week prior to surgery to ensure adequate platelet function recovery given the disruption between collagen and platelet aggregation. Medications can be resumed 3-7 days after achieving postoperative hemostasis, depending on the type of surgery and risk of bleeding.”

As for venetoclax, “prior to surgery, patients should receive granulocyte colony-stimulating factor for neutropenia, blood transfusions for anemia, and platelet transfusions for thrombocytopenia to maintain procedural parameters.”

In the big picture, study lead author Dr. Ma said, “patients with CLL are doing well on continuous targeted treatments, and if there are otherwise no contraindications, they should be considered for procedures to improve their quality of life.”

In an interview, Stanford (Calif.) University surgeon Joe Forrester MD, MSc, who’s familiar with the report findings, said its conclusions are valid. “The nice thing is that a lot of the [CLL] therapies don’t have a lot of surgical side effects. Most should not preclude a patient from going to surgery.”

He advised colleagues to make sure to be open with patients about the heightened surgical risks due to CLL, such when they need emergency procedures. And it’s important to be realistic about whether patients will live long enough to benefit from the rare surgeries – such as weight-loss procedures – that won’t show major benefits for 5-10 years, he said.

The Lymphoma Research Foundation supported the study. Dr. Ma, several coauthors, and Dr. Forrester report no disclosures. One coauthor reports multiple relationships with industry.

As various surgical procedures become more feasible for patients with chronic lymphocytic leukemia (CLL), a team of hematologist-oncologists and cardiologists published a new report advising colleagues to carefully consider the risks and benefits of such operations.

In the past decade, as targeted therapies have permitted better management of CLL, a new realm of possibilities has opened up for patients with this blood cancer.

“Previously, patients may not have been candidates for elective surgeries, such as hip replacements,” said hematologist-oncologist Helen Ma, MD, of the University of Irvine (Calif.) and VA Long Beach Healthcare System. She is the lead author of the report, which appeared in the British Journal of Hematology.

“Now that targeted therapies are controlling CLL well, patients may elect to have procedures that they may not have considered if their blood counts were very low or they felt too unwell to go through such invasive surgeries,” said Dr. Ma in an interview. In fact, the study authors noted that, “with currently available treatments, many patients with CLL are living considerably longer than the 1-year life expectancy threshold that proceduralists require.”

But extra surgical risks persist. “Both CLL and its treatment can increase the risk of complications during and after procedures, though available data are not consistently stratified by stage and whether patients are undergoing treatment,” the report authors noted.

Research has linked CLL to higher rates of blood transfusions in cardiac surgeries: One study, conducted partially in the era of targeted therapy, found that 87% of these surgery patients with CLL needed blood products vs. 65% of those who didn’t have CLL (P = .01). Studies didn’t find any extra risk of infections in patients with CLL, however, and there are conflicting findings about whether hospital mortality is higher.

Another study, also conducted partially in the era of targeted therapy, found that patients with CLL who had percutaneous coronary intervention procedures “developed higher rates of in-hospital mortality, any complication, bleeding and postoperative stroke compared to those seen in patients without leukemia.”

The authors of the new report noted that “patients with more advanced stage are at increased risk of bleeding and thromboembolic events relevant to their disease and invasive procedures.” Patients at more than minimal risk should undergo electrocardiograms prior to cardiac procedures, they wrote. Stress tests, coronary angiography, and percutaneous coronary intervention may also be warranted.

“To optimize evaluation and perioperative management, we strongly recommend the prospective collaborative inclusion of a multidisciplinary team including hematologists/oncologists, cardiologists (ideally cardio-oncologists), surgeons and anesthetists, as well as their ongoing involvement during the postoperative period,” the authors wrote.

As for medications, the researchers said that “generally, antibody therapy has no impact on surgery.” They added, “There is no evidence to hold treatment with anti-CD20 monoclonal antibodies prior to procedures unless the patient has cytopenias that may be a contra-indication. If that is the case, we recommend holding until counts recover to the parameters required for the procedure.”

In regard to Bruton’s tyrosine kinase inhibitors such as ibrutinib, “patients undergoing major surgeries with high risk of bleeding should hold Bruton’s tyrosine kinase inhibitors for a week prior to surgery to ensure adequate platelet function recovery given the disruption between collagen and platelet aggregation. Medications can be resumed 3-7 days after achieving postoperative hemostasis, depending on the type of surgery and risk of bleeding.”

As for venetoclax, “prior to surgery, patients should receive granulocyte colony-stimulating factor for neutropenia, blood transfusions for anemia, and platelet transfusions for thrombocytopenia to maintain procedural parameters.”

In the big picture, study lead author Dr. Ma said, “patients with CLL are doing well on continuous targeted treatments, and if there are otherwise no contraindications, they should be considered for procedures to improve their quality of life.”

In an interview, Stanford (Calif.) University surgeon Joe Forrester MD, MSc, who’s familiar with the report findings, said its conclusions are valid. “The nice thing is that a lot of the [CLL] therapies don’t have a lot of surgical side effects. Most should not preclude a patient from going to surgery.”

He advised colleagues to make sure to be open with patients about the heightened surgical risks due to CLL, such when they need emergency procedures. And it’s important to be realistic about whether patients will live long enough to benefit from the rare surgeries – such as weight-loss procedures – that won’t show major benefits for 5-10 years, he said.

The Lymphoma Research Foundation supported the study. Dr. Ma, several coauthors, and Dr. Forrester report no disclosures. One coauthor reports multiple relationships with industry.

As various surgical procedures become more feasible for patients with chronic lymphocytic leukemia (CLL), a team of hematologist-oncologists and cardiologists published a new report advising colleagues to carefully consider the risks and benefits of such operations.

In the past decade, as targeted therapies have permitted better management of CLL, a new realm of possibilities has opened up for patients with this blood cancer.

“Previously, patients may not have been candidates for elective surgeries, such as hip replacements,” said hematologist-oncologist Helen Ma, MD, of the University of Irvine (Calif.) and VA Long Beach Healthcare System. She is the lead author of the report, which appeared in the British Journal of Hematology.

“Now that targeted therapies are controlling CLL well, patients may elect to have procedures that they may not have considered if their blood counts were very low or they felt too unwell to go through such invasive surgeries,” said Dr. Ma in an interview. In fact, the study authors noted that, “with currently available treatments, many patients with CLL are living considerably longer than the 1-year life expectancy threshold that proceduralists require.”

But extra surgical risks persist. “Both CLL and its treatment can increase the risk of complications during and after procedures, though available data are not consistently stratified by stage and whether patients are undergoing treatment,” the report authors noted.

Research has linked CLL to higher rates of blood transfusions in cardiac surgeries: One study, conducted partially in the era of targeted therapy, found that 87% of these surgery patients with CLL needed blood products vs. 65% of those who didn’t have CLL (P = .01). Studies didn’t find any extra risk of infections in patients with CLL, however, and there are conflicting findings about whether hospital mortality is higher.

Another study, also conducted partially in the era of targeted therapy, found that patients with CLL who had percutaneous coronary intervention procedures “developed higher rates of in-hospital mortality, any complication, bleeding and postoperative stroke compared to those seen in patients without leukemia.”

The authors of the new report noted that “patients with more advanced stage are at increased risk of bleeding and thromboembolic events relevant to their disease and invasive procedures.” Patients at more than minimal risk should undergo electrocardiograms prior to cardiac procedures, they wrote. Stress tests, coronary angiography, and percutaneous coronary intervention may also be warranted.

“To optimize evaluation and perioperative management, we strongly recommend the prospective collaborative inclusion of a multidisciplinary team including hematologists/oncologists, cardiologists (ideally cardio-oncologists), surgeons and anesthetists, as well as their ongoing involvement during the postoperative period,” the authors wrote.

As for medications, the researchers said that “generally, antibody therapy has no impact on surgery.” They added, “There is no evidence to hold treatment with anti-CD20 monoclonal antibodies prior to procedures unless the patient has cytopenias that may be a contra-indication. If that is the case, we recommend holding until counts recover to the parameters required for the procedure.”

In regard to Bruton’s tyrosine kinase inhibitors such as ibrutinib, “patients undergoing major surgeries with high risk of bleeding should hold Bruton’s tyrosine kinase inhibitors for a week prior to surgery to ensure adequate platelet function recovery given the disruption between collagen and platelet aggregation. Medications can be resumed 3-7 days after achieving postoperative hemostasis, depending on the type of surgery and risk of bleeding.”

As for venetoclax, “prior to surgery, patients should receive granulocyte colony-stimulating factor for neutropenia, blood transfusions for anemia, and platelet transfusions for thrombocytopenia to maintain procedural parameters.”

In the big picture, study lead author Dr. Ma said, “patients with CLL are doing well on continuous targeted treatments, and if there are otherwise no contraindications, they should be considered for procedures to improve their quality of life.”

In an interview, Stanford (Calif.) University surgeon Joe Forrester MD, MSc, who’s familiar with the report findings, said its conclusions are valid. “The nice thing is that a lot of the [CLL] therapies don’t have a lot of surgical side effects. Most should not preclude a patient from going to surgery.”

He advised colleagues to make sure to be open with patients about the heightened surgical risks due to CLL, such when they need emergency procedures. And it’s important to be realistic about whether patients will live long enough to benefit from the rare surgeries – such as weight-loss procedures – that won’t show major benefits for 5-10 years, he said.

The Lymphoma Research Foundation supported the study. Dr. Ma, several coauthors, and Dr. Forrester report no disclosures. One coauthor reports multiple relationships with industry.

A new real-world analysis finds that severe infection rates were higher than in clinical trials in 67 patients with chronic lymphocytic leukemia (CLL) or B-cell lymphoma who took ibrutinib (Imbruvica), idelalisib (Zydelig), or venetoclax (Venclexta).

For example, “the rate of severe infection for ibrutinib in clinical trials ranged from 12.8% to 45% with median follow-up ranging from 27 to 65 months. In our study, the rate of severe infection was 45.3% within a shorter median follow-up period of 23.3 months,” said study lead author Amanda Tey, MPharm, a hematology pharmacist with Monash Health in Clayton, Australia, in an interview.

The results suggest that “real-world severe infection risk is higher than previously appreciated,” said Ms. Tey, whose findings were published in the European Journal of Hematology. “Poor performance status and a high comorbidity burden further increase this risk.”

According to the study, there are limited data about real-world infection rates for patients with CLL or B-cell lymphoma who take the three drugs.

Both the underlying blood cancer and the drugs themselves may disrupt the immune system in these patients, Ms. Tey noted. “Ibrutinib inhibits interleukin-2-inducible T-cell kinase, which has a role in T-cell maturation. Idelalisib reduces regulatory T-cell activity and natural killer cell and neutrophil inflammatory responses. Venetoclax is associated with a high rate of neutropenia.”

For the new retrospective, single-center study, researchers tracked adult patients who’d received the drugs from 2014 to 2021 in a hospital network serving 1.5 million people in the Australian state of Victoria. The primary outcome was severe infection of grade 3 or higher. Patients were excluded for such factors as having been primarily treated at other facilities, receiving less than 30 days of treatment, or having been treated for other indications such as primary central nervous system lymphoma.

Of the 67 patients in the study, the numbers taking the drugs were 53 (ibrutinib), 8 (idelalisib), and 6 (venetoclax). Eleven patients took more than one drug. Median age was 73 years, and 73% of patients were male.

Patients spent a median 23.3, 4.8, and 3.5 months taking ibrutinib, idelalisib, and venetoclax, respectively, before treatment stopped or data were collected. Patients were commonly prescribed antimicrobials to prevent pneumocystis jirovecii pneumonia and herpes simplex virus (HSV)/varicella zoster virus (VZV) infection.

Researchers found that 48% of the patients had at least one serious infection: 45% of those on ibrutinib, 63% of those on idelalisib, and 50% of those on venetoclax. Seven patients died of infections.

In comparison, the researchers reported, a systematic review of idelalisib in blood cancer clinical trials reported an overall infection rate of 28%, while clinical trials reported an infection rate of 17.5%-22% in patients taking venetoclax for CLL.

Poor performance status and higher levels of comorbidity were linked to higher risk of infection, and infections occurred at a median of 5.4 months.

Lead author Ms. Tey highlighted the fact that most of the patients in the new study had relapsed/refractory disease. The infection risk in the real-world first-line setting is unknown, she said. “Furthermore, due to the size of our study and high uptake of antimicrobial prophylaxis, the optimal prophylaxis strategy for these patients remains unclear.”

In an interview, infectious disease physician Gemma Reynolds, MChD, MPH, of Austin Health and Peter MacCallum Cancer Center in Melbourne, said the study findings reflect “a lot of what we know from other observational studies and clinical practice. There is a risk of infection, and serious infection, associated with these agents. Sometimes the pathogen is classically opportunistic, but often it is bacterial, and respiratory sites are common. Infections often occur early into a course of therapy.”

Dr. Reynolds, who didn’t take part in the study, urged colleagues to cast a wide net if a patient appears to have an infection but doesn’t respond to conventional therapies such as antibiotics. “Unusual infections are possible,” she said, and aggressive early workups may be advisable via blood cultures, viral swabs, sputum culture, early imaging, bronchoscopy, and preemptive monitoring in patients with a prior infection history with a disease such as CMV.

Alessandra Ferrajoli, MD, a hematologist/oncologist at MD Anderson Cancer Center who also didn’t take part in the study, agreed in an interview that the findings reflect those found in other reports. “It should be highlighted that the population studied is at particular high risk for infections given the high proportion of patients with recurrent disease (85%), many patients with concurrent hypogammaglobulinemia (64%), and the patient median age of 73 years and a high comorbidities burden,” she said. “In my view, this explains the higher rate of infections reported in this study, when compared to other case series.”

Dr. Ferrajoli added that there’s no standard antimicrobial prophylaxis for patients with B-cell malignancies receiving targeted therapies. “Anti-HSV/VZV prophylaxis is commonly implemented. Additional antiviral, antimicrobial, and antifungal prophylaxis should be used based on patients’ absolute neutrophil and T-cell count and individual risk factors, including prior history of infections such as CMV, prior splenectomy, and history of invasive fungal infections.”

The study was funded by Monash Health, the National Health and Medical Research Council (Australia), and the Society of Hospital Pharmacists of Australia. Ms. Tey reported no disclosures. Some of the study authors reported multiple disclosures. Dr. Reynolds discloses a PhD scholarship from the National Health and Medical Research Council. Dr. Ferrajoli reported no disclosures.

A new real-world analysis finds that severe infection rates were higher than in clinical trials in 67 patients with chronic lymphocytic leukemia (CLL) or B-cell lymphoma who took ibrutinib (Imbruvica), idelalisib (Zydelig), or venetoclax (Venclexta).

For example, “the rate of severe infection for ibrutinib in clinical trials ranged from 12.8% to 45% with median follow-up ranging from 27 to 65 months. In our study, the rate of severe infection was 45.3% within a shorter median follow-up period of 23.3 months,” said study lead author Amanda Tey, MPharm, a hematology pharmacist with Monash Health in Clayton, Australia, in an interview.

The results suggest that “real-world severe infection risk is higher than previously appreciated,” said Ms. Tey, whose findings were published in the European Journal of Hematology. “Poor performance status and a high comorbidity burden further increase this risk.”

According to the study, there are limited data about real-world infection rates for patients with CLL or B-cell lymphoma who take the three drugs.

Both the underlying blood cancer and the drugs themselves may disrupt the immune system in these patients, Ms. Tey noted. “Ibrutinib inhibits interleukin-2-inducible T-cell kinase, which has a role in T-cell maturation. Idelalisib reduces regulatory T-cell activity and natural killer cell and neutrophil inflammatory responses. Venetoclax is associated with a high rate of neutropenia.”

For the new retrospective, single-center study, researchers tracked adult patients who’d received the drugs from 2014 to 2021 in a hospital network serving 1.5 million people in the Australian state of Victoria. The primary outcome was severe infection of grade 3 or higher. Patients were excluded for such factors as having been primarily treated at other facilities, receiving less than 30 days of treatment, or having been treated for other indications such as primary central nervous system lymphoma.

Of the 67 patients in the study, the numbers taking the drugs were 53 (ibrutinib), 8 (idelalisib), and 6 (venetoclax). Eleven patients took more than one drug. Median age was 73 years, and 73% of patients were male.

Patients spent a median 23.3, 4.8, and 3.5 months taking ibrutinib, idelalisib, and venetoclax, respectively, before treatment stopped or data were collected. Patients were commonly prescribed antimicrobials to prevent pneumocystis jirovecii pneumonia and herpes simplex virus (HSV)/varicella zoster virus (VZV) infection.

Researchers found that 48% of the patients had at least one serious infection: 45% of those on ibrutinib, 63% of those on idelalisib, and 50% of those on venetoclax. Seven patients died of infections.

In comparison, the researchers reported, a systematic review of idelalisib in blood cancer clinical trials reported an overall infection rate of 28%, while clinical trials reported an infection rate of 17.5%-22% in patients taking venetoclax for CLL.

Poor performance status and higher levels of comorbidity were linked to higher risk of infection, and infections occurred at a median of 5.4 months.

Lead author Ms. Tey highlighted the fact that most of the patients in the new study had relapsed/refractory disease. The infection risk in the real-world first-line setting is unknown, she said. “Furthermore, due to the size of our study and high uptake of antimicrobial prophylaxis, the optimal prophylaxis strategy for these patients remains unclear.”

In an interview, infectious disease physician Gemma Reynolds, MChD, MPH, of Austin Health and Peter MacCallum Cancer Center in Melbourne, said the study findings reflect “a lot of what we know from other observational studies and clinical practice. There is a risk of infection, and serious infection, associated with these agents. Sometimes the pathogen is classically opportunistic, but often it is bacterial, and respiratory sites are common. Infections often occur early into a course of therapy.”

Dr. Reynolds, who didn’t take part in the study, urged colleagues to cast a wide net if a patient appears to have an infection but doesn’t respond to conventional therapies such as antibiotics. “Unusual infections are possible,” she said, and aggressive early workups may be advisable via blood cultures, viral swabs, sputum culture, early imaging, bronchoscopy, and preemptive monitoring in patients with a prior infection history with a disease such as CMV.

Alessandra Ferrajoli, MD, a hematologist/oncologist at MD Anderson Cancer Center who also didn’t take part in the study, agreed in an interview that the findings reflect those found in other reports. “It should be highlighted that the population studied is at particular high risk for infections given the high proportion of patients with recurrent disease (85%), many patients with concurrent hypogammaglobulinemia (64%), and the patient median age of 73 years and a high comorbidities burden,” she said. “In my view, this explains the higher rate of infections reported in this study, when compared to other case series.”

Dr. Ferrajoli added that there’s no standard antimicrobial prophylaxis for patients with B-cell malignancies receiving targeted therapies. “Anti-HSV/VZV prophylaxis is commonly implemented. Additional antiviral, antimicrobial, and antifungal prophylaxis should be used based on patients’ absolute neutrophil and T-cell count and individual risk factors, including prior history of infections such as CMV, prior splenectomy, and history of invasive fungal infections.”

The study was funded by Monash Health, the National Health and Medical Research Council (Australia), and the Society of Hospital Pharmacists of Australia. Ms. Tey reported no disclosures. Some of the study authors reported multiple disclosures. Dr. Reynolds discloses a PhD scholarship from the National Health and Medical Research Council. Dr. Ferrajoli reported no disclosures.

A new real-world analysis finds that severe infection rates were higher than in clinical trials in 67 patients with chronic lymphocytic leukemia (CLL) or B-cell lymphoma who took ibrutinib (Imbruvica), idelalisib (Zydelig), or venetoclax (Venclexta).

For example, “the rate of severe infection for ibrutinib in clinical trials ranged from 12.8% to 45% with median follow-up ranging from 27 to 65 months. In our study, the rate of severe infection was 45.3% within a shorter median follow-up period of 23.3 months,” said study lead author Amanda Tey, MPharm, a hematology pharmacist with Monash Health in Clayton, Australia, in an interview.

The results suggest that “real-world severe infection risk is higher than previously appreciated,” said Ms. Tey, whose findings were published in the European Journal of Hematology. “Poor performance status and a high comorbidity burden further increase this risk.”

According to the study, there are limited data about real-world infection rates for patients with CLL or B-cell lymphoma who take the three drugs.

Both the underlying blood cancer and the drugs themselves may disrupt the immune system in these patients, Ms. Tey noted. “Ibrutinib inhibits interleukin-2-inducible T-cell kinase, which has a role in T-cell maturation. Idelalisib reduces regulatory T-cell activity and natural killer cell and neutrophil inflammatory responses. Venetoclax is associated with a high rate of neutropenia.”

For the new retrospective, single-center study, researchers tracked adult patients who’d received the drugs from 2014 to 2021 in a hospital network serving 1.5 million people in the Australian state of Victoria. The primary outcome was severe infection of grade 3 or higher. Patients were excluded for such factors as having been primarily treated at other facilities, receiving less than 30 days of treatment, or having been treated for other indications such as primary central nervous system lymphoma.

Of the 67 patients in the study, the numbers taking the drugs were 53 (ibrutinib), 8 (idelalisib), and 6 (venetoclax). Eleven patients took more than one drug. Median age was 73 years, and 73% of patients were male.

Patients spent a median 23.3, 4.8, and 3.5 months taking ibrutinib, idelalisib, and venetoclax, respectively, before treatment stopped or data were collected. Patients were commonly prescribed antimicrobials to prevent pneumocystis jirovecii pneumonia and herpes simplex virus (HSV)/varicella zoster virus (VZV) infection.

Researchers found that 48% of the patients had at least one serious infection: 45% of those on ibrutinib, 63% of those on idelalisib, and 50% of those on venetoclax. Seven patients died of infections.

In comparison, the researchers reported, a systematic review of idelalisib in blood cancer clinical trials reported an overall infection rate of 28%, while clinical trials reported an infection rate of 17.5%-22% in patients taking venetoclax for CLL.

Poor performance status and higher levels of comorbidity were linked to higher risk of infection, and infections occurred at a median of 5.4 months.

Lead author Ms. Tey highlighted the fact that most of the patients in the new study had relapsed/refractory disease. The infection risk in the real-world first-line setting is unknown, she said. “Furthermore, due to the size of our study and high uptake of antimicrobial prophylaxis, the optimal prophylaxis strategy for these patients remains unclear.”

In an interview, infectious disease physician Gemma Reynolds, MChD, MPH, of Austin Health and Peter MacCallum Cancer Center in Melbourne, said the study findings reflect “a lot of what we know from other observational studies and clinical practice. There is a risk of infection, and serious infection, associated with these agents. Sometimes the pathogen is classically opportunistic, but often it is bacterial, and respiratory sites are common. Infections often occur early into a course of therapy.”

Dr. Reynolds, who didn’t take part in the study, urged colleagues to cast a wide net if a patient appears to have an infection but doesn’t respond to conventional therapies such as antibiotics. “Unusual infections are possible,” she said, and aggressive early workups may be advisable via blood cultures, viral swabs, sputum culture, early imaging, bronchoscopy, and preemptive monitoring in patients with a prior infection history with a disease such as CMV.

Alessandra Ferrajoli, MD, a hematologist/oncologist at MD Anderson Cancer Center who also didn’t take part in the study, agreed in an interview that the findings reflect those found in other reports. “It should be highlighted that the population studied is at particular high risk for infections given the high proportion of patients with recurrent disease (85%), many patients with concurrent hypogammaglobulinemia (64%), and the patient median age of 73 years and a high comorbidities burden,” she said. “In my view, this explains the higher rate of infections reported in this study, when compared to other case series.”

Dr. Ferrajoli added that there’s no standard antimicrobial prophylaxis for patients with B-cell malignancies receiving targeted therapies. “Anti-HSV/VZV prophylaxis is commonly implemented. Additional antiviral, antimicrobial, and antifungal prophylaxis should be used based on patients’ absolute neutrophil and T-cell count and individual risk factors, including prior history of infections such as CMV, prior splenectomy, and history of invasive fungal infections.”

The study was funded by Monash Health, the National Health and Medical Research Council (Australia), and the Society of Hospital Pharmacists of Australia. Ms. Tey reported no disclosures. Some of the study authors reported multiple disclosures. Dr. Reynolds discloses a PhD scholarship from the National Health and Medical Research Council. Dr. Ferrajoli reported no disclosures.

One therapy that has transformed the management of this disease is anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. Currently there are three FDA-approved options for patients with relapsed/refractory large B-cell lymphoma (LBCL) who have received at least two prior lines of therapy.^[1-3] More recently, axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) have also been approved for second-line therapy on the basis of results of the ZUMA-7 and TRANSFORM studies, respectively.^[4,5]The primary analysis of the TRANSFORM study, which included patients with primary refractory or early relapse of large B-cell lymphoma, is now available. In this study, 184 patients were randomly assigned to receive liso-cel or three cycles of the standard of care (high-dose chemotherapy and autologous stem cell transplantation). After a 17.5-month median follow-up, the liso-cel vs standard-of-care group had significantly improved median event-free survival (hazard ratio [HR] 0.356; 95% CI 0.243-0.522), median progression-free survival (HR 0.400; P < .0001), and complete response rate (74% vs 43%; P < .0001), along with low rates of grade 3 cytokine release syndrome (1%) and neurologic events (4%). This confirms the role of liso-cel in the second-line setting for high-risk patients.

Another promising treatment approach across lymphoma subtypes, including DLBCL, are CD20/CD3 bispecific monoclonal antibodies. The results of the phase 2 trial of glofitamab for patients with relapsed/refractory DLBCL were published recently. This study included 155 patients with relapsed/refractory DLBCL after at least two prior lines of therapy. Approximately one third of patients had received prior CAR T-cell therapy. Patients were treated for a fixed duration of 12 cycles. At a median follow-up of 12.6 months, 39% (95% CI 32%-48%) and 52% (95% CI 43%-60%) of patients achieved complete and objective responses, respectively. Seventy-eight percent of patients with a complete response continued to be in remission at 12 months. Grade 3 or higher cytokine release syndrome was rare and occurred in less than 5% of patients.

Bispecific antibodies have many advantages, including off-the-shelf access and favorable toxicity profiles. Longer follow-up, however, will be required to determine the durability of response beyond 1 year. As bispecific antibodies become available, many questions will emerge, including how best to sequence with CAR T-cell therapy and whether to combine them with other regimens. Additional studies of bispecific antibodies in combination with chemoimmunotherapy and other treatment approaches are underway.

Additional References

1.         Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531-2544. Doi:10.1056/NEJMoa1707447

2.         Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380:45-56. Doi:10.1056/NEJMoa1804980

3.         Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study. Lancet. 2020;396:839-852. Doi:10.1016/S0140-6736(20)31366-0

4.         Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. Doi:10.1056/NEJMoa2116133

5.         Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): Results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399:2294-2308. Doi:10.1016/S0140-6736(22)00662-6

One therapy that has transformed the management of this disease is anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. Currently there are three FDA-approved options for patients with relapsed/refractory large B-cell lymphoma (LBCL) who have received at least two prior lines of therapy.^[1-3] More recently, axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) have also been approved for second-line therapy on the basis of results of the ZUMA-7 and TRANSFORM studies, respectively.^[4,5]The primary analysis of the TRANSFORM study, which included patients with primary refractory or early relapse of large B-cell lymphoma, is now available. In this study, 184 patients were randomly assigned to receive liso-cel or three cycles of the standard of care (high-dose chemotherapy and autologous stem cell transplantation). After a 17.5-month median follow-up, the liso-cel vs standard-of-care group had significantly improved median event-free survival (hazard ratio [HR] 0.356; 95% CI 0.243-0.522), median progression-free survival (HR 0.400; P < .0001), and complete response rate (74% vs 43%; P < .0001), along with low rates of grade 3 cytokine release syndrome (1%) and neurologic events (4%). This confirms the role of liso-cel in the second-line setting for high-risk patients.

Another promising treatment approach across lymphoma subtypes, including DLBCL, are CD20/CD3 bispecific monoclonal antibodies. The results of the phase 2 trial of glofitamab for patients with relapsed/refractory DLBCL were published recently. This study included 155 patients with relapsed/refractory DLBCL after at least two prior lines of therapy. Approximately one third of patients had received prior CAR T-cell therapy. Patients were treated for a fixed duration of 12 cycles. At a median follow-up of 12.6 months, 39% (95% CI 32%-48%) and 52% (95% CI 43%-60%) of patients achieved complete and objective responses, respectively. Seventy-eight percent of patients with a complete response continued to be in remission at 12 months. Grade 3 or higher cytokine release syndrome was rare and occurred in less than 5% of patients.

Bispecific antibodies have many advantages, including off-the-shelf access and favorable toxicity profiles. Longer follow-up, however, will be required to determine the durability of response beyond 1 year. As bispecific antibodies become available, many questions will emerge, including how best to sequence with CAR T-cell therapy and whether to combine them with other regimens. Additional studies of bispecific antibodies in combination with chemoimmunotherapy and other treatment approaches are underway.

Additional References

1.         Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531-2544. Doi:10.1056/NEJMoa1707447

2.         Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380:45-56. Doi:10.1056/NEJMoa1804980

3.         Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study. Lancet. 2020;396:839-852. Doi:10.1016/S0140-6736(20)31366-0

4.         Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. Doi:10.1056/NEJMoa2116133

5.         Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): Results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399:2294-2308. Doi:10.1016/S0140-6736(22)00662-6

One therapy that has transformed the management of this disease is anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. Currently there are three FDA-approved options for patients with relapsed/refractory large B-cell lymphoma (LBCL) who have received at least two prior lines of therapy.^[1-3] More recently, axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) have also been approved for second-line therapy on the basis of results of the ZUMA-7 and TRANSFORM studies, respectively.^[4,5]The primary analysis of the TRANSFORM study, which included patients with primary refractory or early relapse of large B-cell lymphoma, is now available. In this study, 184 patients were randomly assigned to receive liso-cel or three cycles of the standard of care (high-dose chemotherapy and autologous stem cell transplantation). After a 17.5-month median follow-up, the liso-cel vs standard-of-care group had significantly improved median event-free survival (hazard ratio [HR] 0.356; 95% CI 0.243-0.522), median progression-free survival (HR 0.400; P < .0001), and complete response rate (74% vs 43%; P < .0001), along with low rates of grade 3 cytokine release syndrome (1%) and neurologic events (4%). This confirms the role of liso-cel in the second-line setting for high-risk patients.

Another promising treatment approach across lymphoma subtypes, including DLBCL, are CD20/CD3 bispecific monoclonal antibodies. The results of the phase 2 trial of glofitamab for patients with relapsed/refractory DLBCL were published recently. This study included 155 patients with relapsed/refractory DLBCL after at least two prior lines of therapy. Approximately one third of patients had received prior CAR T-cell therapy. Patients were treated for a fixed duration of 12 cycles. At a median follow-up of 12.6 months, 39% (95% CI 32%-48%) and 52% (95% CI 43%-60%) of patients achieved complete and objective responses, respectively. Seventy-eight percent of patients with a complete response continued to be in remission at 12 months. Grade 3 or higher cytokine release syndrome was rare and occurred in less than 5% of patients.

Bispecific antibodies have many advantages, including off-the-shelf access and favorable toxicity profiles. Longer follow-up, however, will be required to determine the durability of response beyond 1 year. As bispecific antibodies become available, many questions will emerge, including how best to sequence with CAR T-cell therapy and whether to combine them with other regimens. Additional studies of bispecific antibodies in combination with chemoimmunotherapy and other treatment approaches are underway.

Additional References

1.         Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531-2544. Doi:10.1056/NEJMoa1707447

2.         Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380:45-56. Doi:10.1056/NEJMoa1804980

3.         Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study. Lancet. 2020;396:839-852. Doi:10.1016/S0140-6736(20)31366-0

4.         Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. Doi:10.1056/NEJMoa2116133

5.         Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): Results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399:2294-2308. Doi:10.1016/S0140-6736(22)00662-6

Mantle cell lymphoma (MCL) has served as a paradigm of progress among the non-Hodgkin lymphomas over the past 30 years. It was originally defined within the Kiel classification as centrocytic lymphoma, then renamed MCL once the characteristic translocation and resulting cyclin D1 overexpression were identified. These diagnostic markers allowed for the characterization of MCL subtypes as well as the initiation of MCL-focused clinical trials which, in turn, led to regulatory approval of more effective regimens, new therapeutic agents, and an improvement in overall survival (OS) from around 3 years to more than 10 years for many patients.

Despite this progress, virtually all patients relapse, and a cure remains elusive for most. In younger (< 65 to 70 years), medically-fit patients who are transplant-eligible and have symptomatic MCL, a standard of care has been induction chemoimmunotherapy containing high-dose cytarabine followed by ASCT consolidation. For example, a clinical trial of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) alternating with R-DHAP (rituximab, dexamethasone, high-dose cytarabine, cisplatin; 3 cycles each) showed a significant benefit over R-CHOP x 6 cycles; at a median follow-up of 10.6 years, the time-to-treatment failure was 8.4 v 3.9 years. In another trial, all patients received induction R-DHAP (with cisplatin or an alternative platinum agent) x 4 cycles followed by ASCT. Those patients randomized to post-ASCT maintenance rituximab for 3 years had significantly improved, 4-year progression-free survival (PFS) as compared with observation only (83% vs 64%, p < 0.001); maintenance also significantly improved OS. 

Although ASCT consolidation followed by maintenance became widely adopted on the basis of these and other clinical trials, important questions remain:

• First, MCL is biologically and clinically quite heterogeneous. Several prognostic tools such as the MCL International Prognostic Index (MIPI) scoring system and biomarkers are available to define lower- versus higher-risk subtypes, but none is routinely used for treatment planning. About 15% of MCL patients present with a highly-aggressive blastoid or pleomorphic variant that usually carries a TP53 mutation or deletion. Given the short survival and limited benefit from dose-intensive chemotherapy and ASCT in TP53-mutated MCL, should transplant be avoided in these patients?    

• Second, if deep remission is achieved following front-line therapy, defined as positron emission tomography (PET) negative and measurable residual disease (MRD) negative, will high-dose chemotherapy and ASCT provide additional benefits or only toxicity?  This question is being addressed by the ongoing ECOG 4151 study, a risk-adapted trial in which post-induction MRD-negative patients are randomized to standard ASCT consolidation plus maintenance rituximab vs maintenance only. 

Bruton tyrosine kinase inhibitors (BTKi) are now among the most used agents for relapsed MCL. Recent clinical trials testing the integration of a BTKi into first- or second-line therapy have shown increased response rates and variable clinical outcomes and toxicities for the combinations, depending upon the chemotherapy- and non-chemotherapy backbones utilized, as well as the BTKi. Combinations with the BCL2 inhibitor venetoclax plus chemotherapy or BTKi are also showing promise.

The activity of BTKi in MCL led the European MCL Network (EMCL) to design the 3-arm TRIANGLE study to analyze the potential of ibrutinib to improve outcomes when given in conjunction with standard ASCT consolidation, and the ability to replace the need for ASCT. The TRIANGLE results were presented by Dr. Martin Dreyling in the Plenary Session at the December 2022 American Society of Hematology (ASH) Annual Meeting. Transplant-eligible MCL patients < 65 years of age were randomized to the EMCL’s established front-line therapy of alternating R-CHOP/R-DHAP plus ASCT; the same regimen plus oral ibrutinib given with the R-CHOP induction cycles and then post-ASCT ibrutinib maintenance therapy for 2 years (Arm A+I); or the A+I regimen minus ASCT (Arm I). Maintenance rituximab was allowed in each arm, on the basis of the treating centers’ institutional guidelines. Overall, 54%-58% of patients in each study arm received rituximab maintenance, with no differential benefit in efficacy noted for those so treated. 

The results showed that 94%-98% of patients responded by the end of induction (defined as R-chemo and ASCT), with complete remissions in 36%-45% (from computerized tomography imaging, not PET scan). With a median follow-up of 31 months, failure-free survival (FFS; the primary study endpoint) was significantly improved for A+I vs A (3 year FFS of 88% vs 72%, respectively; p = 0.0008). In a subgroup analysis, FFS was notably improved for A+I in patients with high-level TP53 overexpression by immunohistochemistry. Toxicity did not differ during the induction and ASCT periods among the 3 arms regarding cytopenia, gastrointestinal disorders, and infections. However, neutropenia and infections were increased in the ibrutinib-containing arms during maintenance therapy—especially for Arm A+I. 

The authors concluded that ASCT plus ibrutinib (Arm A+I) is superior to ASCT only (Arm A), and that Arm A is not superior to ibrutinib without ASCT (Arm I). No decision can yet be made regarding A+I versus I for which FFS to date remains very similar; however, the authors favor ibrutinib without ASCT due to lower toxicity. OS is trending to favor the ibrutinib arms, but longer follow-up will be needed to fully assess.

Should ASCT consolidation now be replaced by ibrutinib-containing induction R-CHOP/R-DHAP and maintenance ibrutinib, with or without maintenance rituximab? A definitive answer will require the fully-published TRIANGLE results, as well as ongoing analysis with longer follow-up. However, it seems very likely that ASCT indeed will be replaced by the new approach. TP53-mutated MCL should be treated with ibrutinib plus R-CHOP/R-DHAP and ibrutinib maintenance as validated in this trial. 

Many centers have begun using a second-generation BTKi, acalabrutinib or zanubrutinib, rather than ibrutinib due to equivalent response rates with more favorable side effect profiles and fewer treatment discontinuations. Caution is warranted regarding simply adding a BTKi to one’s favored MCL induction regimen and foregoing ASCT—pending additional studies and the safety of such alternative approaches. 

These are indeed exciting times of therapeutic progress, as they have been improving outcomes and providing longer survival outcomes for MCL patients. Targeted agents facilitate this shift to less intensive and chemotherapy-free regimens that provide enhanced response and mitigate short- and longer-term toxicities. More results will be forthcoming for MRD as a treatment endpoint, guiding maintenance therapy, and for risk-adapted treatment of newly-diagnosed and relapsing patients (based upon MCL subtype and biomarker profiles). Enrolling patients into clinical trials is strongly encouraged as the best mechanism to help answer emerging questions in the field and open the pathway to continued progress.

Mantle cell lymphoma (MCL) has served as a paradigm of progress among the non-Hodgkin lymphomas over the past 30 years. It was originally defined within the Kiel classification as centrocytic lymphoma, then renamed MCL once the characteristic translocation and resulting cyclin D1 overexpression were identified. These diagnostic markers allowed for the characterization of MCL subtypes as well as the initiation of MCL-focused clinical trials which, in turn, led to regulatory approval of more effective regimens, new therapeutic agents, and an improvement in overall survival (OS) from around 3 years to more than 10 years for many patients.

Despite this progress, virtually all patients relapse, and a cure remains elusive for most. In younger (< 65 to 70 years), medically-fit patients who are transplant-eligible and have symptomatic MCL, a standard of care has been induction chemoimmunotherapy containing high-dose cytarabine followed by ASCT consolidation. For example, a clinical trial of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) alternating with R-DHAP (rituximab, dexamethasone, high-dose cytarabine, cisplatin; 3 cycles each) showed a significant benefit over R-CHOP x 6 cycles; at a median follow-up of 10.6 years, the time-to-treatment failure was 8.4 v 3.9 years. In another trial, all patients received induction R-DHAP (with cisplatin or an alternative platinum agent) x 4 cycles followed by ASCT. Those patients randomized to post-ASCT maintenance rituximab for 3 years had significantly improved, 4-year progression-free survival (PFS) as compared with observation only (83% vs 64%, p < 0.001); maintenance also significantly improved OS. 

Although ASCT consolidation followed by maintenance became widely adopted on the basis of these and other clinical trials, important questions remain:

• First, MCL is biologically and clinically quite heterogeneous. Several prognostic tools such as the MCL International Prognostic Index (MIPI) scoring system and biomarkers are available to define lower- versus higher-risk subtypes, but none is routinely used for treatment planning. About 15% of MCL patients present with a highly-aggressive blastoid or pleomorphic variant that usually carries a TP53 mutation or deletion. Given the short survival and limited benefit from dose-intensive chemotherapy and ASCT in TP53-mutated MCL, should transplant be avoided in these patients?    

• Second, if deep remission is achieved following front-line therapy, defined as positron emission tomography (PET) negative and measurable residual disease (MRD) negative, will high-dose chemotherapy and ASCT provide additional benefits or only toxicity?  This question is being addressed by the ongoing ECOG 4151 study, a risk-adapted trial in which post-induction MRD-negative patients are randomized to standard ASCT consolidation plus maintenance rituximab vs maintenance only. 

Bruton tyrosine kinase inhibitors (BTKi) are now among the most used agents for relapsed MCL. Recent clinical trials testing the integration of a BTKi into first- or second-line therapy have shown increased response rates and variable clinical outcomes and toxicities for the combinations, depending upon the chemotherapy- and non-chemotherapy backbones utilized, as well as the BTKi. Combinations with the BCL2 inhibitor venetoclax plus chemotherapy or BTKi are also showing promise.

The activity of BTKi in MCL led the European MCL Network (EMCL) to design the 3-arm TRIANGLE study to analyze the potential of ibrutinib to improve outcomes when given in conjunction with standard ASCT consolidation, and the ability to replace the need for ASCT. The TRIANGLE results were presented by Dr. Martin Dreyling in the Plenary Session at the December 2022 American Society of Hematology (ASH) Annual Meeting. Transplant-eligible MCL patients < 65 years of age were randomized to the EMCL’s established front-line therapy of alternating R-CHOP/R-DHAP plus ASCT; the same regimen plus oral ibrutinib given with the R-CHOP induction cycles and then post-ASCT ibrutinib maintenance therapy for 2 years (Arm A+I); or the A+I regimen minus ASCT (Arm I). Maintenance rituximab was allowed in each arm, on the basis of the treating centers’ institutional guidelines. Overall, 54%-58% of patients in each study arm received rituximab maintenance, with no differential benefit in efficacy noted for those so treated. 

The results showed that 94%-98% of patients responded by the end of induction (defined as R-chemo and ASCT), with complete remissions in 36%-45% (from computerized tomography imaging, not PET scan). With a median follow-up of 31 months, failure-free survival (FFS; the primary study endpoint) was significantly improved for A+I vs A (3 year FFS of 88% vs 72%, respectively; p = 0.0008). In a subgroup analysis, FFS was notably improved for A+I in patients with high-level TP53 overexpression by immunohistochemistry. Toxicity did not differ during the induction and ASCT periods among the 3 arms regarding cytopenia, gastrointestinal disorders, and infections. However, neutropenia and infections were increased in the ibrutinib-containing arms during maintenance therapy—especially for Arm A+I. 

The authors concluded that ASCT plus ibrutinib (Arm A+I) is superior to ASCT only (Arm A), and that Arm A is not superior to ibrutinib without ASCT (Arm I). No decision can yet be made regarding A+I versus I for which FFS to date remains very similar; however, the authors favor ibrutinib without ASCT due to lower toxicity. OS is trending to favor the ibrutinib arms, but longer follow-up will be needed to fully assess.

Should ASCT consolidation now be replaced by ibrutinib-containing induction R-CHOP/R-DHAP and maintenance ibrutinib, with or without maintenance rituximab? A definitive answer will require the fully-published TRIANGLE results, as well as ongoing analysis with longer follow-up. However, it seems very likely that ASCT indeed will be replaced by the new approach. TP53-mutated MCL should be treated with ibrutinib plus R-CHOP/R-DHAP and ibrutinib maintenance as validated in this trial. 

Many centers have begun using a second-generation BTKi, acalabrutinib or zanubrutinib, rather than ibrutinib due to equivalent response rates with more favorable side effect profiles and fewer treatment discontinuations. Caution is warranted regarding simply adding a BTKi to one’s favored MCL induction regimen and foregoing ASCT—pending additional studies and the safety of such alternative approaches. 

These are indeed exciting times of therapeutic progress, as they have been improving outcomes and providing longer survival outcomes for MCL patients. Targeted agents facilitate this shift to less intensive and chemotherapy-free regimens that provide enhanced response and mitigate short- and longer-term toxicities. More results will be forthcoming for MRD as a treatment endpoint, guiding maintenance therapy, and for risk-adapted treatment of newly-diagnosed and relapsing patients (based upon MCL subtype and biomarker profiles). Enrolling patients into clinical trials is strongly encouraged as the best mechanism to help answer emerging questions in the field and open the pathway to continued progress.

Mantle cell lymphoma (MCL) has served as a paradigm of progress among the non-Hodgkin lymphomas over the past 30 years. It was originally defined within the Kiel classification as centrocytic lymphoma, then renamed MCL once the characteristic translocation and resulting cyclin D1 overexpression were identified. These diagnostic markers allowed for the characterization of MCL subtypes as well as the initiation of MCL-focused clinical trials which, in turn, led to regulatory approval of more effective regimens, new therapeutic agents, and an improvement in overall survival (OS) from around 3 years to more than 10 years for many patients.

Despite this progress, virtually all patients relapse, and a cure remains elusive for most. In younger (< 65 to 70 years), medically-fit patients who are transplant-eligible and have symptomatic MCL, a standard of care has been induction chemoimmunotherapy containing high-dose cytarabine followed by ASCT consolidation. For example, a clinical trial of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) alternating with R-DHAP (rituximab, dexamethasone, high-dose cytarabine, cisplatin; 3 cycles each) showed a significant benefit over R-CHOP x 6 cycles; at a median follow-up of 10.6 years, the time-to-treatment failure was 8.4 v 3.9 years. In another trial, all patients received induction R-DHAP (with cisplatin or an alternative platinum agent) x 4 cycles followed by ASCT. Those patients randomized to post-ASCT maintenance rituximab for 3 years had significantly improved, 4-year progression-free survival (PFS) as compared with observation only (83% vs 64%, p < 0.001); maintenance also significantly improved OS. 

Although ASCT consolidation followed by maintenance became widely adopted on the basis of these and other clinical trials, important questions remain:

• First, MCL is biologically and clinically quite heterogeneous. Several prognostic tools such as the MCL International Prognostic Index (MIPI) scoring system and biomarkers are available to define lower- versus higher-risk subtypes, but none is routinely used for treatment planning. About 15% of MCL patients present with a highly-aggressive blastoid or pleomorphic variant that usually carries a TP53 mutation or deletion. Given the short survival and limited benefit from dose-intensive chemotherapy and ASCT in TP53-mutated MCL, should transplant be avoided in these patients?    

• Second, if deep remission is achieved following front-line therapy, defined as positron emission tomography (PET) negative and measurable residual disease (MRD) negative, will high-dose chemotherapy and ASCT provide additional benefits or only toxicity?  This question is being addressed by the ongoing ECOG 4151 study, a risk-adapted trial in which post-induction MRD-negative patients are randomized to standard ASCT consolidation plus maintenance rituximab vs maintenance only. 

Bruton tyrosine kinase inhibitors (BTKi) are now among the most used agents for relapsed MCL. Recent clinical trials testing the integration of a BTKi into first- or second-line therapy have shown increased response rates and variable clinical outcomes and toxicities for the combinations, depending upon the chemotherapy- and non-chemotherapy backbones utilized, as well as the BTKi. Combinations with the BCL2 inhibitor venetoclax plus chemotherapy or BTKi are also showing promise.

The activity of BTKi in MCL led the European MCL Network (EMCL) to design the 3-arm TRIANGLE study to analyze the potential of ibrutinib to improve outcomes when given in conjunction with standard ASCT consolidation, and the ability to replace the need for ASCT. The TRIANGLE results were presented by Dr. Martin Dreyling in the Plenary Session at the December 2022 American Society of Hematology (ASH) Annual Meeting. Transplant-eligible MCL patients < 65 years of age were randomized to the EMCL’s established front-line therapy of alternating R-CHOP/R-DHAP plus ASCT; the same regimen plus oral ibrutinib given with the R-CHOP induction cycles and then post-ASCT ibrutinib maintenance therapy for 2 years (Arm A+I); or the A+I regimen minus ASCT (Arm I). Maintenance rituximab was allowed in each arm, on the basis of the treating centers’ institutional guidelines. Overall, 54%-58% of patients in each study arm received rituximab maintenance, with no differential benefit in efficacy noted for those so treated. 

The results showed that 94%-98% of patients responded by the end of induction (defined as R-chemo and ASCT), with complete remissions in 36%-45% (from computerized tomography imaging, not PET scan). With a median follow-up of 31 months, failure-free survival (FFS; the primary study endpoint) was significantly improved for A+I vs A (3 year FFS of 88% vs 72%, respectively; p = 0.0008). In a subgroup analysis, FFS was notably improved for A+I in patients with high-level TP53 overexpression by immunohistochemistry. Toxicity did not differ during the induction and ASCT periods among the 3 arms regarding cytopenia, gastrointestinal disorders, and infections. However, neutropenia and infections were increased in the ibrutinib-containing arms during maintenance therapy—especially for Arm A+I. 

The authors concluded that ASCT plus ibrutinib (Arm A+I) is superior to ASCT only (Arm A), and that Arm A is not superior to ibrutinib without ASCT (Arm I). No decision can yet be made regarding A+I versus I for which FFS to date remains very similar; however, the authors favor ibrutinib without ASCT due to lower toxicity. OS is trending to favor the ibrutinib arms, but longer follow-up will be needed to fully assess.

Should ASCT consolidation now be replaced by ibrutinib-containing induction R-CHOP/R-DHAP and maintenance ibrutinib, with or without maintenance rituximab? A definitive answer will require the fully-published TRIANGLE results, as well as ongoing analysis with longer follow-up. However, it seems very likely that ASCT indeed will be replaced by the new approach. TP53-mutated MCL should be treated with ibrutinib plus R-CHOP/R-DHAP and ibrutinib maintenance as validated in this trial. 

Many centers have begun using a second-generation BTKi, acalabrutinib or zanubrutinib, rather than ibrutinib due to equivalent response rates with more favorable side effect profiles and fewer treatment discontinuations. Caution is warranted regarding simply adding a BTKi to one’s favored MCL induction regimen and foregoing ASCT—pending additional studies and the safety of such alternative approaches. 

These are indeed exciting times of therapeutic progress, as they have been improving outcomes and providing longer survival outcomes for MCL patients. Targeted agents facilitate this shift to less intensive and chemotherapy-free regimens that provide enhanced response and mitigate short- and longer-term toxicities. More results will be forthcoming for MRD as a treatment endpoint, guiding maintenance therapy, and for risk-adapted treatment of newly-diagnosed and relapsing patients (based upon MCL subtype and biomarker profiles). Enrolling patients into clinical trials is strongly encouraged as the best mechanism to help answer emerging questions in the field and open the pathway to continued progress.

Key clinical point: Diagnosis to treatment interval (DTI; time in days from the diagnosis date to therapy initiation) is strongly associated with poor survival outcomes in patients with newly diagnosed mantle cell lymphoma (MCL).

Major finding: Patients with a short vs long DTI had significantly shorter median overall (7.8 vs 11.8 years) and progression-free (2.5 vs 4.8 years) survival (both log-rank P < .0001). A short vs long DTI was associated with significantly poorer overall (adjusted hazard ratio [aHR] 1.57) and progression-free (aHR 1.50) survival (both P < .001).

Study details: This pooled analysis of three large datasets included 1097 patients with newly diagnosed MCL and available DTI data, of which 300 had a short (0-14 days) and 797 had a long (15-60 days) DTI.

Disclosures: One of the datasets, Molecular Epidemiology Resource, was supported by grants from the US National Cancer Institute. Some authors reported ties with various organizations.

Source: Epperla N et al. Impact of diagnosis to treatment interval in patients with newly diagnosed mantle cell lymphoma. Blood Adv. 2022 (Dec 14). Doi: 10.1182/bloodadvances.2022009225

Key clinical point: Diagnosis to treatment interval (DTI; time in days from the diagnosis date to therapy initiation) is strongly associated with poor survival outcomes in patients with newly diagnosed mantle cell lymphoma (MCL).

Major finding: Patients with a short vs long DTI had significantly shorter median overall (7.8 vs 11.8 years) and progression-free (2.5 vs 4.8 years) survival (both log-rank P < .0001). A short vs long DTI was associated with significantly poorer overall (adjusted hazard ratio [aHR] 1.57) and progression-free (aHR 1.50) survival (both P < .001).

Study details: This pooled analysis of three large datasets included 1097 patients with newly diagnosed MCL and available DTI data, of which 300 had a short (0-14 days) and 797 had a long (15-60 days) DTI.

Disclosures: One of the datasets, Molecular Epidemiology Resource, was supported by grants from the US National Cancer Institute. Some authors reported ties with various organizations.

Source: Epperla N et al. Impact of diagnosis to treatment interval in patients with newly diagnosed mantle cell lymphoma. Blood Adv. 2022 (Dec 14). Doi: 10.1182/bloodadvances.2022009225

Key clinical point: Diagnosis to treatment interval (DTI; time in days from the diagnosis date to therapy initiation) is strongly associated with poor survival outcomes in patients with newly diagnosed mantle cell lymphoma (MCL).

Major finding: Patients with a short vs long DTI had significantly shorter median overall (7.8 vs 11.8 years) and progression-free (2.5 vs 4.8 years) survival (both log-rank P < .0001). A short vs long DTI was associated with significantly poorer overall (adjusted hazard ratio [aHR] 1.57) and progression-free (aHR 1.50) survival (both P < .001).

Study details: This pooled analysis of three large datasets included 1097 patients with newly diagnosed MCL and available DTI data, of which 300 had a short (0-14 days) and 797 had a long (15-60 days) DTI.

Disclosures: One of the datasets, Molecular Epidemiology Resource, was supported by grants from the US National Cancer Institute. Some authors reported ties with various organizations.

Source: Epperla N et al. Impact of diagnosis to treatment interval in patients with newly diagnosed mantle cell lymphoma. Blood Adv. 2022 (Dec 14). Doi: 10.1182/bloodadvances.2022009225

Key clinical point: Low natural killer (NK) cell counts (NKCC; <100 cells/μL) at diagnosis predict poor outcomes in patients with diffuse large B-cell lymphoma (DLBCL), and lenalidomide maintenance therapy has no impact on this unfavorable prognosis.

Major finding: Low baseline NKCC were associated with shorter progression-free (hazard ratio [HR] 2.2) and overall (HR 2.8) survival (both P < .001), independently of age-adjusted International Prognostic Index scores, and with a higher risk for progression or relapse (P = .0025). Lenalidomide maintenance therapy did not affect the prognostic value of low NKCC at diagnosis or random assignment (P = .6349).

Study details: This prospective ancillary study of the REMARC trial included 335 elderly patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone who underwent flow cytometric peripheral blood lymphocyte analysis at diagnosis, at random assignment to the lenalidomide or placebo arm, or at 6 months after random assignment.

Disclosures: This study was funded by Celgene. Some authors reported ties with various organizations, including Celgene.

Source: Beldi-Ferchiou A et al. Lenalidomide maintenance fails to overcome the unfavourable prognosis of low NK-cell counts in rituximab–chemotherapy responsive elderly DLBCL patients: A LYSA group study. Br J Haematol. 2023 (Feb 6). Doi: 10.1111/bjh.18642

Key clinical point: Low natural killer (NK) cell counts (NKCC; <100 cells/μL) at diagnosis predict poor outcomes in patients with diffuse large B-cell lymphoma (DLBCL), and lenalidomide maintenance therapy has no impact on this unfavorable prognosis.

Major finding: Low baseline NKCC were associated with shorter progression-free (hazard ratio [HR] 2.2) and overall (HR 2.8) survival (both P < .001), independently of age-adjusted International Prognostic Index scores, and with a higher risk for progression or relapse (P = .0025). Lenalidomide maintenance therapy did not affect the prognostic value of low NKCC at diagnosis or random assignment (P = .6349).

Study details: This prospective ancillary study of the REMARC trial included 335 elderly patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone who underwent flow cytometric peripheral blood lymphocyte analysis at diagnosis, at random assignment to the lenalidomide or placebo arm, or at 6 months after random assignment.

Disclosures: This study was funded by Celgene. Some authors reported ties with various organizations, including Celgene.

Source: Beldi-Ferchiou A et al. Lenalidomide maintenance fails to overcome the unfavourable prognosis of low NK-cell counts in rituximab–chemotherapy responsive elderly DLBCL patients: A LYSA group study. Br J Haematol. 2023 (Feb 6). Doi: 10.1111/bjh.18642

Key clinical point: Low natural killer (NK) cell counts (NKCC; <100 cells/μL) at diagnosis predict poor outcomes in patients with diffuse large B-cell lymphoma (DLBCL), and lenalidomide maintenance therapy has no impact on this unfavorable prognosis.

Major finding: Low baseline NKCC were associated with shorter progression-free (hazard ratio [HR] 2.2) and overall (HR 2.8) survival (both P < .001), independently of age-adjusted International Prognostic Index scores, and with a higher risk for progression or relapse (P = .0025). Lenalidomide maintenance therapy did not affect the prognostic value of low NKCC at diagnosis or random assignment (P = .6349).

Study details: This prospective ancillary study of the REMARC trial included 335 elderly patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone who underwent flow cytometric peripheral blood lymphocyte analysis at diagnosis, at random assignment to the lenalidomide or placebo arm, or at 6 months after random assignment.

Disclosures: This study was funded by Celgene. Some authors reported ties with various organizations, including Celgene.

Source: Beldi-Ferchiou A et al. Lenalidomide maintenance fails to overcome the unfavourable prognosis of low NK-cell counts in rituximab–chemotherapy responsive elderly DLBCL patients: A LYSA group study. Br J Haematol. 2023 (Feb 6). Doi: 10.1111/bjh.18642

Key clinical point: Ibrutinib continued to benefit most treatment-naive patients (58%) with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in the RESONATE-2 study for ≥5 years, irrespective of baseline characteristics.

Major finding: At a median follow-up of 89.2 months, the median progression-free survival (PFS) and overall survival (OS) were not reached; the 7-year PFS and OS rates were 82% and 94%, respectively. Complete response rates increased from 10% at 1 year to 42% at 5 years and 46% at 7 years. No new safety signals were observed.

Study details: This study analyzed the data of 79 treatment-naive patients aged ≥65 years with CLL or SLL who were randomly assigned to receive ibrutinib in the phase 3 RESONATE-2 trial and its extension study and had continued the treatment for ≥5 years.

Disclosures: This study was sponsored by Pharmacyclics LLC, an AbbVie Company. Some authors reported ties with various organizations, including Pharmacyclics. Two authors declared being employees of, holding stocks in, or having other ownership interests in Pharmacyclics/AbbVie.

Source: Woyach JA et al. Characteristics and clinical outcomes of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma receiving ibrutinib for ≥5 years in the RESONATE-2 study. Cancers (Basel). 2023;15(2):507 (Jan 13). Doi: 10.3390/cancers15020507

Key clinical point: Ibrutinib continued to benefit most treatment-naive patients (58%) with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in the RESONATE-2 study for ≥5 years, irrespective of baseline characteristics.

Major finding: At a median follow-up of 89.2 months, the median progression-free survival (PFS) and overall survival (OS) were not reached; the 7-year PFS and OS rates were 82% and 94%, respectively. Complete response rates increased from 10% at 1 year to 42% at 5 years and 46% at 7 years. No new safety signals were observed.

Study details: This study analyzed the data of 79 treatment-naive patients aged ≥65 years with CLL or SLL who were randomly assigned to receive ibrutinib in the phase 3 RESONATE-2 trial and its extension study and had continued the treatment for ≥5 years.

Disclosures: This study was sponsored by Pharmacyclics LLC, an AbbVie Company. Some authors reported ties with various organizations, including Pharmacyclics. Two authors declared being employees of, holding stocks in, or having other ownership interests in Pharmacyclics/AbbVie.

Source: Woyach JA et al. Characteristics and clinical outcomes of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma receiving ibrutinib for ≥5 years in the RESONATE-2 study. Cancers (Basel). 2023;15(2):507 (Jan 13). Doi: 10.3390/cancers15020507

Key clinical point: Ibrutinib continued to benefit most treatment-naive patients (58%) with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in the RESONATE-2 study for ≥5 years, irrespective of baseline characteristics.

Major finding: At a median follow-up of 89.2 months, the median progression-free survival (PFS) and overall survival (OS) were not reached; the 7-year PFS and OS rates were 82% and 94%, respectively. Complete response rates increased from 10% at 1 year to 42% at 5 years and 46% at 7 years. No new safety signals were observed.

Study details: This study analyzed the data of 79 treatment-naive patients aged ≥65 years with CLL or SLL who were randomly assigned to receive ibrutinib in the phase 3 RESONATE-2 trial and its extension study and had continued the treatment for ≥5 years.

Disclosures: This study was sponsored by Pharmacyclics LLC, an AbbVie Company. Some authors reported ties with various organizations, including Pharmacyclics. Two authors declared being employees of, holding stocks in, or having other ownership interests in Pharmacyclics/AbbVie.

Source: Woyach JA et al. Characteristics and clinical outcomes of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma receiving ibrutinib for ≥5 years in the RESONATE-2 study. Cancers (Basel). 2023;15(2):507 (Jan 13). Doi: 10.3390/cancers15020507

Key clinical point: Autologous stem cell transplantation (ASCT) leads to high durable remission rates in patients with relapsed follicular lymphoma (FL), with the functional cure rate elucidated by long-term follow-up being >50%.

Major finding: At a median follow-up of 12.5 years, the 12-year time-to-progression (TTP), time-to-next-treatment, progression-free survival, and overall survival rates were 57% (95% CI 49%-65%), 61% (95% CI 52%-69%), 51% (95% CI 42%-59%), and 69% (95% CI 60%-76%), respectively. The TTP curve achieved a plateau at 57% starting 9 years after ASCT with no relapses after this timepoint; 10 patients remained alive without recurrence for ≥20 years after ASCT.

Study details: This retrospective multicenter study included 162 adult patients with relapsed FL who underwent ASCT.

Disclosures: This study did not receive any funding. Some authors declared receiving honoraria from various sources.

Source: Puckrin R et al. Long-term follow-up demonstrates curative potential of autologous stem cell transplantation for relapsed follicular lymphoma. Br J Haematol. 2023 (Jan 10). Doi: 10.1111/bjh.18640

Key clinical point: Autologous stem cell transplantation (ASCT) leads to high durable remission rates in patients with relapsed follicular lymphoma (FL), with the functional cure rate elucidated by long-term follow-up being >50%.

Major finding: At a median follow-up of 12.5 years, the 12-year time-to-progression (TTP), time-to-next-treatment, progression-free survival, and overall survival rates were 57% (95% CI 49%-65%), 61% (95% CI 52%-69%), 51% (95% CI 42%-59%), and 69% (95% CI 60%-76%), respectively. The TTP curve achieved a plateau at 57% starting 9 years after ASCT with no relapses after this timepoint; 10 patients remained alive without recurrence for ≥20 years after ASCT.

Study details: This retrospective multicenter study included 162 adult patients with relapsed FL who underwent ASCT.

Disclosures: This study did not receive any funding. Some authors declared receiving honoraria from various sources.

Source: Puckrin R et al. Long-term follow-up demonstrates curative potential of autologous stem cell transplantation for relapsed follicular lymphoma. Br J Haematol. 2023 (Jan 10). Doi: 10.1111/bjh.18640

Key clinical point: Autologous stem cell transplantation (ASCT) leads to high durable remission rates in patients with relapsed follicular lymphoma (FL), with the functional cure rate elucidated by long-term follow-up being >50%.

Major finding: At a median follow-up of 12.5 years, the 12-year time-to-progression (TTP), time-to-next-treatment, progression-free survival, and overall survival rates were 57% (95% CI 49%-65%), 61% (95% CI 52%-69%), 51% (95% CI 42%-59%), and 69% (95% CI 60%-76%), respectively. The TTP curve achieved a plateau at 57% starting 9 years after ASCT with no relapses after this timepoint; 10 patients remained alive without recurrence for ≥20 years after ASCT.

Study details: This retrospective multicenter study included 162 adult patients with relapsed FL who underwent ASCT.

Disclosures: This study did not receive any funding. Some authors declared receiving honoraria from various sources.

Source: Puckrin R et al. Long-term follow-up demonstrates curative potential of autologous stem cell transplantation for relapsed follicular lymphoma. Br J Haematol. 2023 (Jan 10). Doi: 10.1111/bjh.18640

Key clinical point: Second-line lisocabtagene maraleucel (liso-cel) offers better efficacy over standard of care (SOC; platinum-based immunochemotherapy followed by high-dose chemotherapy+autologous stem cell transplantation [ASCT]) in chemotherapy-sensitive patients with relapsed/refractory large B-cell lymphoma (LBCL) along with a favorable safety profile.

Major finding: After a 17.5-month median follow-up, the liso-cel vs SOC group had significantly improved median event-free survival (hazard ratio [HR] 0.356; 95% CI 0.243-0.522), median progression-free survival (HR 0.400; P < .0001), and complete response rate (74% vs 43%; P < .0001), along with low grade 3 cytokine release syndrome (1%) and neurological event (4%) rates.

Study details: This phase 3 study, TRANSFORM, included 184 adult patients with relapsed/refractory LBCL who were eligible for high-dose chemotherapy+ASCT and were randomly assigned to receive liso-cel (100×10⁶ chimeric antigen receptor-positive T cells) or three cycles of SOC.

Disclosures: This study was funded by Celgene, a Bristol-Myers Squibb Company. Some authors reported ties with various organizations, including Celgene. Three authors declared being employees of Celgene.

Source: Abramson JS et al. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: Primary analysis of phase 3 TRANSFORM study. Blood. 2022 (Dec 21). Doi: 10.1182/blood.2022018730

Key clinical point: Second-line lisocabtagene maraleucel (liso-cel) offers better efficacy over standard of care (SOC; platinum-based immunochemotherapy followed by high-dose chemotherapy+autologous stem cell transplantation [ASCT]) in chemotherapy-sensitive patients with relapsed/refractory large B-cell lymphoma (LBCL) along with a favorable safety profile.

Major finding: After a 17.5-month median follow-up, the liso-cel vs SOC group had significantly improved median event-free survival (hazard ratio [HR] 0.356; 95% CI 0.243-0.522), median progression-free survival (HR 0.400; P < .0001), and complete response rate (74% vs 43%; P < .0001), along with low grade 3 cytokine release syndrome (1%) and neurological event (4%) rates.

Study details: This phase 3 study, TRANSFORM, included 184 adult patients with relapsed/refractory LBCL who were eligible for high-dose chemotherapy+ASCT and were randomly assigned to receive liso-cel (100×10⁶ chimeric antigen receptor-positive T cells) or three cycles of SOC.

Disclosures: This study was funded by Celgene, a Bristol-Myers Squibb Company. Some authors reported ties with various organizations, including Celgene. Three authors declared being employees of Celgene.

Source: Abramson JS et al. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: Primary analysis of phase 3 TRANSFORM study. Blood. 2022 (Dec 21). Doi: 10.1182/blood.2022018730

Key clinical point: Second-line lisocabtagene maraleucel (liso-cel) offers better efficacy over standard of care (SOC; platinum-based immunochemotherapy followed by high-dose chemotherapy+autologous stem cell transplantation [ASCT]) in chemotherapy-sensitive patients with relapsed/refractory large B-cell lymphoma (LBCL) along with a favorable safety profile.

Major finding: After a 17.5-month median follow-up, the liso-cel vs SOC group had significantly improved median event-free survival (hazard ratio [HR] 0.356; 95% CI 0.243-0.522), median progression-free survival (HR 0.400; P < .0001), and complete response rate (74% vs 43%; P < .0001), along with low grade 3 cytokine release syndrome (1%) and neurological event (4%) rates.

Study details: This phase 3 study, TRANSFORM, included 184 adult patients with relapsed/refractory LBCL who were eligible for high-dose chemotherapy+ASCT and were randomly assigned to receive liso-cel (100×10⁶ chimeric antigen receptor-positive T cells) or three cycles of SOC.

Disclosures: This study was funded by Celgene, a Bristol-Myers Squibb Company. Some authors reported ties with various organizations, including Celgene. Three authors declared being employees of Celgene.

Source: Abramson JS et al. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: Primary analysis of phase 3 TRANSFORM study. Blood. 2022 (Dec 21). Doi: 10.1182/blood.2022018730