HONOLULU – The diversity of species in the sputum of patients undergoing therapy for nontuberculosis mycobacterial pulmonary disease (NTM-PD) could be a marker for treatment efficacy, authors of a small prospective study suggest.

Neil Osterweil/MDedge

Among 14 patients treated for NTM-PD, 7 of whom had treatment-refractory disease and 7 of whom had microbiological cures after antibiotic therapy, the diversity of the microbiome in sputum was greater for those patients who were cured, indicating that the variety of species found in sputum during treatment could help clinicians evaluate the efficacy of therapy and guide patient management, said Noeul Kang, MD, PhD, from Samsung Medical Center in Seoul, South Korea.

“What we found was that in NTM-PD patients, the sputum of the patients who remained in long-time stabilization without recurrence exhibited higher microbiome diversity than that of treatment-refractory patients, and several genera were identified in the samples of the cured group. We hope to do more research on this, and we are planning to compare the patients who have never been treated with those who respond to treatment,” she said at the annual meeting of the American College of Chest Physicians (CHEST).
 

NTM-PD on the rise

The incidence and prevalence of NTM-PD in both South Korea and the United States have been rising steadily since 2007, with the highest incidence occurring among those 65 and older.

“NTM-PD is becoming a global burden,” Dr. Kang said.

Across the world the most commonly occurring organisms in NTM-PD patients are Mycobacterium avium complex (MAC), with other mycobacteria species varying in frequency by region.

Outcomes of treatment differ according to the etiologic organism, with M. avium complex infections being successfully treated in about 60% of patients, compared with 70% of patients’ infections with the M. abscessus massiliense, and 30%-40% of infections yielding to antibiotics in patients with M. abscessus abscessus, Dr. Kang said.

To compare the characteristics of the sputum microbiota of NTM-PD patients based on their treatment outcomes, Dr. Kang and colleagues looked at sputum from all patients with NTM-PD who agreed to provide samples at their center from 2018 through 2022.

After excluding those who did not receive antibiotics, those who were on treatment but did not have refractory disease, and those who were lost to follow-up or whose samples did not pass quality control, they identified seven patients who had microbiological cures, and seven whose disease remained refractory to treatment.

They defined culture conversion at three or more consecutive negative sputum cultures after treatment, collected at least 4 weeks apart, and microbiological cures at maintenance of multiple consecutive negative cultures without any positive cultures of the causative species from respiratory samples.

Infections were deemed to be refractory if there were sustained positive cultures from respiratory samples of causative NTM species after at least 1 year of antibiotic therapy.
 

Diversity analysis

Samples from 8 of the 14 participants had M. abscessus-PD, with the proportion higher among those who had a sustained microbiological cure (71.4% vs. 42.9%).

At baseline, patients with refractory disease were found to have significantly lower alpha diversity, a measure of microbial diversity within a single sample, compared with those whose infections were cured (P = .025).

In addition, samples at 6-month follow-up from those with baseline ­refractory infections ­had differences in the species level of beta-diversity (that is, differences among samples), compared with both baseline and follow-up samples from the cured group (P = .022 and .024, respectively).

The investigators also used linear discriminant analysis to look at taxonomic biomarkers, and observed that several species were more abundant in samples from the microbiological cure group than from the refractory disease group (P < .05) These species included organisms in the Streptococcus pneumoniae group, Prevotella melaninogenica, and Haemophilus parahaemolyticus group.
 

Promising start

A pulmonologist who was not involved in the study commented in an interview that, although the findings need further study, the microbiome of sputum samples has the potential for predictive value.

“I think this will be clinically useful, actually, if we’re able to identify and diagnose patients with MAC disease and then we identify their sputum microbiome, it might give us an idea whether these patients are more sensitive or refractory to treatment,” said Muhammad U. Khawar, MD, from the University of Cincinnati.

Dr. Khawar moderated the session where Dr. Kang reported her data.

The investigators did not report a funding source. Dr. Kang and Dr. Khawar reported that they had no relevant disclosures.
 

HONOLULU – The diversity of species in the sputum of patients undergoing therapy for nontuberculosis mycobacterial pulmonary disease (NTM-PD) could be a marker for treatment efficacy, authors of a small prospective study suggest.

Neil Osterweil/MDedge

Among 14 patients treated for NTM-PD, 7 of whom had treatment-refractory disease and 7 of whom had microbiological cures after antibiotic therapy, the diversity of the microbiome in sputum was greater for those patients who were cured, indicating that the variety of species found in sputum during treatment could help clinicians evaluate the efficacy of therapy and guide patient management, said Noeul Kang, MD, PhD, from Samsung Medical Center in Seoul, South Korea.

“What we found was that in NTM-PD patients, the sputum of the patients who remained in long-time stabilization without recurrence exhibited higher microbiome diversity than that of treatment-refractory patients, and several genera were identified in the samples of the cured group. We hope to do more research on this, and we are planning to compare the patients who have never been treated with those who respond to treatment,” she said at the annual meeting of the American College of Chest Physicians (CHEST).
 

NTM-PD on the rise

The incidence and prevalence of NTM-PD in both South Korea and the United States have been rising steadily since 2007, with the highest incidence occurring among those 65 and older.

“NTM-PD is becoming a global burden,” Dr. Kang said.

Across the world the most commonly occurring organisms in NTM-PD patients are Mycobacterium avium complex (MAC), with other mycobacteria species varying in frequency by region.

Outcomes of treatment differ according to the etiologic organism, with M. avium complex infections being successfully treated in about 60% of patients, compared with 70% of patients’ infections with the M. abscessus massiliense, and 30%-40% of infections yielding to antibiotics in patients with M. abscessus abscessus, Dr. Kang said.

To compare the characteristics of the sputum microbiota of NTM-PD patients based on their treatment outcomes, Dr. Kang and colleagues looked at sputum from all patients with NTM-PD who agreed to provide samples at their center from 2018 through 2022.

After excluding those who did not receive antibiotics, those who were on treatment but did not have refractory disease, and those who were lost to follow-up or whose samples did not pass quality control, they identified seven patients who had microbiological cures, and seven whose disease remained refractory to treatment.

They defined culture conversion at three or more consecutive negative sputum cultures after treatment, collected at least 4 weeks apart, and microbiological cures at maintenance of multiple consecutive negative cultures without any positive cultures of the causative species from respiratory samples.

Infections were deemed to be refractory if there were sustained positive cultures from respiratory samples of causative NTM species after at least 1 year of antibiotic therapy.
 

Diversity analysis

Samples from 8 of the 14 participants had M. abscessus-PD, with the proportion higher among those who had a sustained microbiological cure (71.4% vs. 42.9%).

At baseline, patients with refractory disease were found to have significantly lower alpha diversity, a measure of microbial diversity within a single sample, compared with those whose infections were cured (P = .025).

In addition, samples at 6-month follow-up from those with baseline ­refractory infections ­had differences in the species level of beta-diversity (that is, differences among samples), compared with both baseline and follow-up samples from the cured group (P = .022 and .024, respectively).

The investigators also used linear discriminant analysis to look at taxonomic biomarkers, and observed that several species were more abundant in samples from the microbiological cure group than from the refractory disease group (P < .05) These species included organisms in the Streptococcus pneumoniae group, Prevotella melaninogenica, and Haemophilus parahaemolyticus group.
 

Promising start

A pulmonologist who was not involved in the study commented in an interview that, although the findings need further study, the microbiome of sputum samples has the potential for predictive value.

“I think this will be clinically useful, actually, if we’re able to identify and diagnose patients with MAC disease and then we identify their sputum microbiome, it might give us an idea whether these patients are more sensitive or refractory to treatment,” said Muhammad U. Khawar, MD, from the University of Cincinnati.

Dr. Khawar moderated the session where Dr. Kang reported her data.

The investigators did not report a funding source. Dr. Kang and Dr. Khawar reported that they had no relevant disclosures.
 

HONOLULU – The diversity of species in the sputum of patients undergoing therapy for nontuberculosis mycobacterial pulmonary disease (NTM-PD) could be a marker for treatment efficacy, authors of a small prospective study suggest.

Neil Osterweil/MDedge

Among 14 patients treated for NTM-PD, 7 of whom had treatment-refractory disease and 7 of whom had microbiological cures after antibiotic therapy, the diversity of the microbiome in sputum was greater for those patients who were cured, indicating that the variety of species found in sputum during treatment could help clinicians evaluate the efficacy of therapy and guide patient management, said Noeul Kang, MD, PhD, from Samsung Medical Center in Seoul, South Korea.

“What we found was that in NTM-PD patients, the sputum of the patients who remained in long-time stabilization without recurrence exhibited higher microbiome diversity than that of treatment-refractory patients, and several genera were identified in the samples of the cured group. We hope to do more research on this, and we are planning to compare the patients who have never been treated with those who respond to treatment,” she said at the annual meeting of the American College of Chest Physicians (CHEST).
 

NTM-PD on the rise

The incidence and prevalence of NTM-PD in both South Korea and the United States have been rising steadily since 2007, with the highest incidence occurring among those 65 and older.

“NTM-PD is becoming a global burden,” Dr. Kang said.

Across the world the most commonly occurring organisms in NTM-PD patients are Mycobacterium avium complex (MAC), with other mycobacteria species varying in frequency by region.

Outcomes of treatment differ according to the etiologic organism, with M. avium complex infections being successfully treated in about 60% of patients, compared with 70% of patients’ infections with the M. abscessus massiliense, and 30%-40% of infections yielding to antibiotics in patients with M. abscessus abscessus, Dr. Kang said.

To compare the characteristics of the sputum microbiota of NTM-PD patients based on their treatment outcomes, Dr. Kang and colleagues looked at sputum from all patients with NTM-PD who agreed to provide samples at their center from 2018 through 2022.

After excluding those who did not receive antibiotics, those who were on treatment but did not have refractory disease, and those who were lost to follow-up or whose samples did not pass quality control, they identified seven patients who had microbiological cures, and seven whose disease remained refractory to treatment.

They defined culture conversion at three or more consecutive negative sputum cultures after treatment, collected at least 4 weeks apart, and microbiological cures at maintenance of multiple consecutive negative cultures without any positive cultures of the causative species from respiratory samples.

Infections were deemed to be refractory if there were sustained positive cultures from respiratory samples of causative NTM species after at least 1 year of antibiotic therapy.
 

Diversity analysis

Samples from 8 of the 14 participants had M. abscessus-PD, with the proportion higher among those who had a sustained microbiological cure (71.4% vs. 42.9%).

At baseline, patients with refractory disease were found to have significantly lower alpha diversity, a measure of microbial diversity within a single sample, compared with those whose infections were cured (P = .025).

In addition, samples at 6-month follow-up from those with baseline ­refractory infections ­had differences in the species level of beta-diversity (that is, differences among samples), compared with both baseline and follow-up samples from the cured group (P = .022 and .024, respectively).

The investigators also used linear discriminant analysis to look at taxonomic biomarkers, and observed that several species were more abundant in samples from the microbiological cure group than from the refractory disease group (P < .05) These species included organisms in the Streptococcus pneumoniae group, Prevotella melaninogenica, and Haemophilus parahaemolyticus group.
 

Promising start

A pulmonologist who was not involved in the study commented in an interview that, although the findings need further study, the microbiome of sputum samples has the potential for predictive value.

“I think this will be clinically useful, actually, if we’re able to identify and diagnose patients with MAC disease and then we identify their sputum microbiome, it might give us an idea whether these patients are more sensitive or refractory to treatment,” said Muhammad U. Khawar, MD, from the University of Cincinnati.

Dr. Khawar moderated the session where Dr. Kang reported her data.

The investigators did not report a funding source. Dr. Kang and Dr. Khawar reported that they had no relevant disclosures.
 

Sirisha Manyam, DO, shares highlights at the AVAHO 2023 conference, including the keynote address by Under Secretary for Health Shereef Elnahal, MD, and a presentation on the Close to Me program that services veterans residing in rural areas.  

Dr Manyam found Dr Elnahal's address particularly compelling, with its emphasis on not only developing but also retaining an oncologic workforce formidable in its evidence-based approach and determined in its commitment to meet the current and coming challenges of veterans' healthcare.  

Sirisha Manyam, DO, shares highlights at the AVAHO 2023 conference, including the keynote address by Under Secretary for Health Shereef Elnahal, MD, and a presentation on the Close to Me program that services veterans residing in rural areas.  

Dr Manyam found Dr Elnahal's address particularly compelling, with its emphasis on not only developing but also retaining an oncologic workforce formidable in its evidence-based approach and determined in its commitment to meet the current and coming challenges of veterans' healthcare.  

Sirisha Manyam, DO, shares highlights at the AVAHO 2023 conference, including the keynote address by Under Secretary for Health Shereef Elnahal, MD, and a presentation on the Close to Me program that services veterans residing in rural areas.  

Dr Manyam found Dr Elnahal's address particularly compelling, with its emphasis on not only developing but also retaining an oncologic workforce formidable in its evidence-based approach and determined in its commitment to meet the current and coming challenges of veterans' healthcare.  

Soo Park, MD, reflects on the experience of attending the AVAHO 2023 conference and highlights several key takeaways. Dr Park emphasizes the progressive nature of the VA healthcare system, its impact on elevating cancer care for veterans, and the importance of teleoncology in reaching all veterans across the United States.

Dr Park details various presentations, such as the keynote address from Dr Shereef Elnahal, under secretary for health in the US Department of Veterans Affairs, and Dr Michael Kelley's discussion on the significance of clinical pathways for standardized care. Dr Park also highlights learnings from the conference, such as the VA's leadership in research efforts, particularly in prostate and lung cancer.

Soo Park, MD, reflects on the experience of attending the AVAHO 2023 conference and highlights several key takeaways. Dr Park emphasizes the progressive nature of the VA healthcare system, its impact on elevating cancer care for veterans, and the importance of teleoncology in reaching all veterans across the United States.

Dr Park details various presentations, such as the keynote address from Dr Shereef Elnahal, under secretary for health in the US Department of Veterans Affairs, and Dr Michael Kelley's discussion on the significance of clinical pathways for standardized care. Dr Park also highlights learnings from the conference, such as the VA's leadership in research efforts, particularly in prostate and lung cancer.

Soo Park, MD, reflects on the experience of attending the AVAHO 2023 conference and highlights several key takeaways. Dr Park emphasizes the progressive nature of the VA healthcare system, its impact on elevating cancer care for veterans, and the importance of teleoncology in reaching all veterans across the United States.

Dr Park details various presentations, such as the keynote address from Dr Shereef Elnahal, under secretary for health in the US Department of Veterans Affairs, and Dr Michael Kelley's discussion on the significance of clinical pathways for standardized care. Dr Park also highlights learnings from the conference, such as the VA's leadership in research efforts, particularly in prostate and lung cancer.

Timothy O'Brien, MD, highlights several key updates from AVAHO 2023 in the areas of toxin-exposure assessment, cancer screening programs, and the expansion of cancer care delivery to remote areas. 

Dr O'Brien shares notable examples from these areas like the PACT Act for veterans, successful lung cancer screening programs, the availability of new tests that measure minimal residual disease in patients with multiple myeloma, and initiatives like the Close to Me  infusion program to improve healthcare access for veterans in rural areas. 

Timothy O'Brien, MD, highlights several key updates from AVAHO 2023 in the areas of toxin-exposure assessment, cancer screening programs, and the expansion of cancer care delivery to remote areas. 

Dr O'Brien shares notable examples from these areas like the PACT Act for veterans, successful lung cancer screening programs, the availability of new tests that measure minimal residual disease in patients with multiple myeloma, and initiatives like the Close to Me  infusion program to improve healthcare access for veterans in rural areas. 

Timothy O'Brien, MD, highlights several key updates from AVAHO 2023 in the areas of toxin-exposure assessment, cancer screening programs, and the expansion of cancer care delivery to remote areas. 

Dr O'Brien shares notable examples from these areas like the PACT Act for veterans, successful lung cancer screening programs, the availability of new tests that measure minimal residual disease in patients with multiple myeloma, and initiatives like the Close to Me  infusion program to improve healthcare access for veterans in rural areas. 

Key clinical point: Long-term exposure to brominated trihalomethanes (THM) in drinking water and swimming pool water is associated with increased odds of developing chronic lymphocytic leukemia (CLL).

Major finding: The odds of developing CLL increased by 22% for every 10 μg/L increase in the level of brominated THM in drinking water (adjusted odds ratio [aOR] 1.22; 95% CI 1.14-1.31). Swimming pool users vs non-users (swimming pool attendance ≥ 10 times vs < 10 times in life) had significantly increased odds of CLL (aOR 2.38; 95% CI 1.61-3.52).

Study details: This multicentric multicase-control study included 170 patients with CLL (age 20-85 years) and 1442 matched population-based control individuals without CLL.

Disclosures: This study was funded by European Commission grants and others. The authors declared no conflicts of interest.

Source: Donat-Vargas C et al. Lifetime exposure to brominated trihalomethanes in drinking water and swimming pool attendance are associated with chronic lymphocytic leukemia: A multicase-control study in Spain (MCC-Spain). J Expo Sci Environ Epidemiol. 2023 (Sep 19). doi: 10.1038/s41370-023-00600-7

Key clinical point: Long-term exposure to brominated trihalomethanes (THM) in drinking water and swimming pool water is associated with increased odds of developing chronic lymphocytic leukemia (CLL).

Major finding: The odds of developing CLL increased by 22% for every 10 μg/L increase in the level of brominated THM in drinking water (adjusted odds ratio [aOR] 1.22; 95% CI 1.14-1.31). Swimming pool users vs non-users (swimming pool attendance ≥ 10 times vs < 10 times in life) had significantly increased odds of CLL (aOR 2.38; 95% CI 1.61-3.52).

Study details: This multicentric multicase-control study included 170 patients with CLL (age 20-85 years) and 1442 matched population-based control individuals without CLL.

Disclosures: This study was funded by European Commission grants and others. The authors declared no conflicts of interest.

Source: Donat-Vargas C et al. Lifetime exposure to brominated trihalomethanes in drinking water and swimming pool attendance are associated with chronic lymphocytic leukemia: A multicase-control study in Spain (MCC-Spain). J Expo Sci Environ Epidemiol. 2023 (Sep 19). doi: 10.1038/s41370-023-00600-7

Key clinical point: Long-term exposure to brominated trihalomethanes (THM) in drinking water and swimming pool water is associated with increased odds of developing chronic lymphocytic leukemia (CLL).

Major finding: The odds of developing CLL increased by 22% for every 10 μg/L increase in the level of brominated THM in drinking water (adjusted odds ratio [aOR] 1.22; 95% CI 1.14-1.31). Swimming pool users vs non-users (swimming pool attendance ≥ 10 times vs < 10 times in life) had significantly increased odds of CLL (aOR 2.38; 95% CI 1.61-3.52).

Study details: This multicentric multicase-control study included 170 patients with CLL (age 20-85 years) and 1442 matched population-based control individuals without CLL.

Disclosures: This study was funded by European Commission grants and others. The authors declared no conflicts of interest.

Source: Donat-Vargas C et al. Lifetime exposure to brominated trihalomethanes in drinking water and swimming pool attendance are associated with chronic lymphocytic leukemia: A multicase-control study in Spain (MCC-Spain). J Expo Sci Environ Epidemiol. 2023 (Sep 19). doi: 10.1038/s41370-023-00600-7

Key clinical point: Chimeric antigen receptor (CAR) T-cell therapy is effective for and can be safely administered to older patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) despite an increased infection rate.

Major finding: At a median follow-up of 16.3 months, the objective response rate was 67%. Median progression-free and overall survival were 10.3 (95% CI 3.3-not reached) and 28.4 (95% CI 12.4-not reached) months, respectively. Patients age > 70 years and age ≤ 70 years had comparable progression-free (P = .6) and overall (P = .5) survival and comparable incidence rates of immune effector cell-associated neurotoxicity syndrome (P = .19); however, patients age > 70 years vs age ≤ 70 years had higher all-grade infection rates (79% vs 40%, respectively).

Study details: This single-center retrospective study included 66 patients with relapsed or refractory DLBCL who received either tisagenlecleucel or axicabtagene ciloleucel, of whom 21% were age > 70 years.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Trando A et al. Outcomes of chimeric antigen receptor (CAR) T-cell therapy in patients with large B-cell lymphoma (LBCL): A single-institution experience. Cancers. 2023; 15(18):4671 (Sep 21). doi: 10.3390/cancers15184671

Key clinical point: Chimeric antigen receptor (CAR) T-cell therapy is effective for and can be safely administered to older patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) despite an increased infection rate.

Major finding: At a median follow-up of 16.3 months, the objective response rate was 67%. Median progression-free and overall survival were 10.3 (95% CI 3.3-not reached) and 28.4 (95% CI 12.4-not reached) months, respectively. Patients age > 70 years and age ≤ 70 years had comparable progression-free (P = .6) and overall (P = .5) survival and comparable incidence rates of immune effector cell-associated neurotoxicity syndrome (P = .19); however, patients age > 70 years vs age ≤ 70 years had higher all-grade infection rates (79% vs 40%, respectively).

Study details: This single-center retrospective study included 66 patients with relapsed or refractory DLBCL who received either tisagenlecleucel or axicabtagene ciloleucel, of whom 21% were age > 70 years.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Trando A et al. Outcomes of chimeric antigen receptor (CAR) T-cell therapy in patients with large B-cell lymphoma (LBCL): A single-institution experience. Cancers. 2023; 15(18):4671 (Sep 21). doi: 10.3390/cancers15184671

Key clinical point: Chimeric antigen receptor (CAR) T-cell therapy is effective for and can be safely administered to older patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) despite an increased infection rate.

Major finding: At a median follow-up of 16.3 months, the objective response rate was 67%. Median progression-free and overall survival were 10.3 (95% CI 3.3-not reached) and 28.4 (95% CI 12.4-not reached) months, respectively. Patients age > 70 years and age ≤ 70 years had comparable progression-free (P = .6) and overall (P = .5) survival and comparable incidence rates of immune effector cell-associated neurotoxicity syndrome (P = .19); however, patients age > 70 years vs age ≤ 70 years had higher all-grade infection rates (79% vs 40%, respectively).

Study details: This single-center retrospective study included 66 patients with relapsed or refractory DLBCL who received either tisagenlecleucel or axicabtagene ciloleucel, of whom 21% were age > 70 years.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Trando A et al. Outcomes of chimeric antigen receptor (CAR) T-cell therapy in patients with large B-cell lymphoma (LBCL): A single-institution experience. Cancers. 2023; 15(18):4671 (Sep 21). doi: 10.3390/cancers15184671

Key clinical point: Acalabrutinib and zanubrutinib showed similar efficacy and safety profiles in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) after matching observed patient variables that are prognostic or predictive at baseline.

Major finding: Acalabrutinib and zanubrutinib treatments resulted in comparable investigator-assessed progression-free survival outcomes (adjusted hazard ratio 0.90; 95% CI 0.60-1.36) and comparable risks for grade ≥3 adverse events (adjusted odds ratio 0.66; 95% CI 0.41-1.05).

Study details: This unanchored indirect comparison study included patients with relapsed or refractory CLL and matched the individual patient-level data of those who received acalabrutinib in the ASCEND trial (n = 149) with the aggregate data of those who received zanubrutinib in the ALPINE trial (n = 327).

Disclosures: This study was funded by AstraZeneca, USA. Some authors declared serving as consultants, advisors, or speakers for or receiving research funding or consulting fees from various sources, including AstraZeneca. Six authors declared being employees of AstraZeneca, USA, or holding stocks in AstraZeneca.

Source: Kittai AS, Skarbnick A, et al. A matching-adjusted indirect comparison of acalabrutinib versus zanubrutinib in relapsed or refractory chronic lymphocytic leukemia. Am J Hematol. 2023 (Oct 9). doi: 10.1002/ajh.27110

Key clinical point: Acalabrutinib and zanubrutinib showed similar efficacy and safety profiles in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) after matching observed patient variables that are prognostic or predictive at baseline.

Major finding: Acalabrutinib and zanubrutinib treatments resulted in comparable investigator-assessed progression-free survival outcomes (adjusted hazard ratio 0.90; 95% CI 0.60-1.36) and comparable risks for grade ≥3 adverse events (adjusted odds ratio 0.66; 95% CI 0.41-1.05).

Study details: This unanchored indirect comparison study included patients with relapsed or refractory CLL and matched the individual patient-level data of those who received acalabrutinib in the ASCEND trial (n = 149) with the aggregate data of those who received zanubrutinib in the ALPINE trial (n = 327).

Disclosures: This study was funded by AstraZeneca, USA. Some authors declared serving as consultants, advisors, or speakers for or receiving research funding or consulting fees from various sources, including AstraZeneca. Six authors declared being employees of AstraZeneca, USA, or holding stocks in AstraZeneca.

Source: Kittai AS, Skarbnick A, et al. A matching-adjusted indirect comparison of acalabrutinib versus zanubrutinib in relapsed or refractory chronic lymphocytic leukemia. Am J Hematol. 2023 (Oct 9). doi: 10.1002/ajh.27110

Key clinical point: Acalabrutinib and zanubrutinib showed similar efficacy and safety profiles in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) after matching observed patient variables that are prognostic or predictive at baseline.

Major finding: Acalabrutinib and zanubrutinib treatments resulted in comparable investigator-assessed progression-free survival outcomes (adjusted hazard ratio 0.90; 95% CI 0.60-1.36) and comparable risks for grade ≥3 adverse events (adjusted odds ratio 0.66; 95% CI 0.41-1.05).

Study details: This unanchored indirect comparison study included patients with relapsed or refractory CLL and matched the individual patient-level data of those who received acalabrutinib in the ASCEND trial (n = 149) with the aggregate data of those who received zanubrutinib in the ALPINE trial (n = 327).

Disclosures: This study was funded by AstraZeneca, USA. Some authors declared serving as consultants, advisors, or speakers for or receiving research funding or consulting fees from various sources, including AstraZeneca. Six authors declared being employees of AstraZeneca, USA, or holding stocks in AstraZeneca.

Source: Kittai AS, Skarbnick A, et al. A matching-adjusted indirect comparison of acalabrutinib versus zanubrutinib in relapsed or refractory chronic lymphocytic leukemia. Am J Hematol. 2023 (Oct 9). doi: 10.1002/ajh.27110

Key clinical point: High-dose cytarabine (HDAC)-based pre-autologous stem cell transplantation (ASCT) induction regimens were not associated with improved survival but led to higher overall response rates (ORR) and lower rates of early relapses in ASCT-eligible patients with mantle cell lymphoma (MCL).

Major finding: Patients receiving rituximab + HDAC (R-HDAC)-based regimens vs rituximab + cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) had significantly higher ORR (85.9% vs 65.7%; P = .007), lower 24-month progression rates (61.9% vs 80.4%; P = .043), and lower mortality (43.9% vs 68.6%; P = .004). However, the 2-year overall survival rates were similar between the R-HADC + ASCT and R-CHOP + ASCT groups (88.7% and 78.8%, respectively; P = .289).

Study details: This retrospective single-center study included 165 ASCT-eligible adult patients with MCL, of whom 136 patients received pre-ASCT induction immunochemotherapy with R-CHOP-like or regimens based on R-HDAC and 50 patients received consolidation with high-dose therapy and ASCT.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: de Pádua Covas Lage LA et al. Up-front ASCT overcomes the survival benefit provided by HDAC-based induction regimens in mantle cell lymphoma: Data from a real-life and long-term cohort. Cancers. 2023; 15(19):4759 (Sep 28). doi: 10.3390/cancers15194759

Key clinical point: High-dose cytarabine (HDAC)-based pre-autologous stem cell transplantation (ASCT) induction regimens were not associated with improved survival but led to higher overall response rates (ORR) and lower rates of early relapses in ASCT-eligible patients with mantle cell lymphoma (MCL).

Major finding: Patients receiving rituximab + HDAC (R-HDAC)-based regimens vs rituximab + cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) had significantly higher ORR (85.9% vs 65.7%; P = .007), lower 24-month progression rates (61.9% vs 80.4%; P = .043), and lower mortality (43.9% vs 68.6%; P = .004). However, the 2-year overall survival rates were similar between the R-HADC + ASCT and R-CHOP + ASCT groups (88.7% and 78.8%, respectively; P = .289).

Study details: This retrospective single-center study included 165 ASCT-eligible adult patients with MCL, of whom 136 patients received pre-ASCT induction immunochemotherapy with R-CHOP-like or regimens based on R-HDAC and 50 patients received consolidation with high-dose therapy and ASCT.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: de Pádua Covas Lage LA et al. Up-front ASCT overcomes the survival benefit provided by HDAC-based induction regimens in mantle cell lymphoma: Data from a real-life and long-term cohort. Cancers. 2023; 15(19):4759 (Sep 28). doi: 10.3390/cancers15194759

Key clinical point: High-dose cytarabine (HDAC)-based pre-autologous stem cell transplantation (ASCT) induction regimens were not associated with improved survival but led to higher overall response rates (ORR) and lower rates of early relapses in ASCT-eligible patients with mantle cell lymphoma (MCL).

Major finding: Patients receiving rituximab + HDAC (R-HDAC)-based regimens vs rituximab + cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) had significantly higher ORR (85.9% vs 65.7%; P = .007), lower 24-month progression rates (61.9% vs 80.4%; P = .043), and lower mortality (43.9% vs 68.6%; P = .004). However, the 2-year overall survival rates were similar between the R-HADC + ASCT and R-CHOP + ASCT groups (88.7% and 78.8%, respectively; P = .289).

Study details: This retrospective single-center study included 165 ASCT-eligible adult patients with MCL, of whom 136 patients received pre-ASCT induction immunochemotherapy with R-CHOP-like or regimens based on R-HDAC and 50 patients received consolidation with high-dose therapy and ASCT.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: de Pádua Covas Lage LA et al. Up-front ASCT overcomes the survival benefit provided by HDAC-based induction regimens in mantle cell lymphoma: Data from a real-life and long-term cohort. Cancers. 2023; 15(19):4759 (Sep 28). doi: 10.3390/cancers15194759

Key clinical point: Cumulative airborne dioxin exposure is significantly associated with an increased risk for non-Hodgkin's lymphoma (NHL), particularly for combined chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

Major finding: A significant association was observed between log-transformed cumulative dioxin exposure index scores and the risk for NHL (adjusted odds ratio [aOR] 1.2; 95% CI 1.0-1.4), especially in case of the CLL and SLL subtypes (aOR 1.6; 95% CI 1.1-2.3), for a 4.4 log µg-toxic equivalent quantity/m² increase corresponding to a standard deviation.

Study details: This case-control study was nested within the prospective French National Institute for Health and Medical Research E3N cohort and included 368 women with NHL and 368 matched control women without NHL.

Disclosures: The E3N cohort was established and maintained with the support of the Mutuelle Générale de l'Education Nationale, France, and other sources. The authors declared no conflicts of interest.

Source: Gaspard E et al. Association between cumulative airborne dioxin exposure and non-Hodgkin's lymphoma risk in a nested case-control study within the French E3N cohort. Sci Total Environ. 2023;906:167330 (Sep 29). doi: 10.1016/j.scitotenv.2023.167330

Key clinical point: Cumulative airborne dioxin exposure is significantly associated with an increased risk for non-Hodgkin's lymphoma (NHL), particularly for combined chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

Major finding: A significant association was observed between log-transformed cumulative dioxin exposure index scores and the risk for NHL (adjusted odds ratio [aOR] 1.2; 95% CI 1.0-1.4), especially in case of the CLL and SLL subtypes (aOR 1.6; 95% CI 1.1-2.3), for a 4.4 log µg-toxic equivalent quantity/m² increase corresponding to a standard deviation.

Study details: This case-control study was nested within the prospective French National Institute for Health and Medical Research E3N cohort and included 368 women with NHL and 368 matched control women without NHL.

Disclosures: The E3N cohort was established and maintained with the support of the Mutuelle Générale de l'Education Nationale, France, and other sources. The authors declared no conflicts of interest.

Source: Gaspard E et al. Association between cumulative airborne dioxin exposure and non-Hodgkin's lymphoma risk in a nested case-control study within the French E3N cohort. Sci Total Environ. 2023;906:167330 (Sep 29). doi: 10.1016/j.scitotenv.2023.167330

Key clinical point: Cumulative airborne dioxin exposure is significantly associated with an increased risk for non-Hodgkin's lymphoma (NHL), particularly for combined chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

Major finding: A significant association was observed between log-transformed cumulative dioxin exposure index scores and the risk for NHL (adjusted odds ratio [aOR] 1.2; 95% CI 1.0-1.4), especially in case of the CLL and SLL subtypes (aOR 1.6; 95% CI 1.1-2.3), for a 4.4 log µg-toxic equivalent quantity/m² increase corresponding to a standard deviation.

Study details: This case-control study was nested within the prospective French National Institute for Health and Medical Research E3N cohort and included 368 women with NHL and 368 matched control women without NHL.

Disclosures: The E3N cohort was established and maintained with the support of the Mutuelle Générale de l'Education Nationale, France, and other sources. The authors declared no conflicts of interest.

Source: Gaspard E et al. Association between cumulative airborne dioxin exposure and non-Hodgkin's lymphoma risk in a nested case-control study within the French E3N cohort. Sci Total Environ. 2023;906:167330 (Sep 29). doi: 10.1016/j.scitotenv.2023.167330

Key clinical point: The ibrutinib + bortezomib combination shows durable efficacy and manageable safety in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL), including high-risk patients.

Major finding: The combination led to an objective response rate of 81.8% (90% CI 71.1%-89.8%), which increased to 87.3% (90% CI 77.4%-93.9%) with ibrutinib maintenance. At a 25.4-month median follow-up, the median duration of response and progression-free survival were 22.7 (95% CI 12.3-not achieved) and 18.6 (95% CI 12.5-not achieved) months, respectively. The adverse event profile was consistent with the known safety profiles of individual drugs.

Study details: This phase 2 trial included 55 ibrutinib-naive and bortezomib-naive patients with R/R MCL previously treated with ≤2 lines of chemotherapy (of whom 75.6% had ≥1 high-risk features) who received 6 cycles of ibrutinib + bortezomib followed by ibrutinib maintenance.

Disclosures: This study was supported by Janssen and others. Some authors declared serving on the advisory boards of or receiving research funding, consulting fees, honoraria, or meeting or travel support from various sources, including Janssen.

Source: Novak U et al. Combined therapy with ibrutinib and bortezomib followed by ibrutinib maintenance in relapsed or refractory mantle cell lymphoma and high-risk features: A phase 1/2 trial of the European MCL network (SAKK 36/13). EClinicalMedicine. 2023;64:102221 (Sep 21). doi: 10.1016/j.eclinm.2023.102221

Key clinical point: The ibrutinib + bortezomib combination shows durable efficacy and manageable safety in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL), including high-risk patients.

Major finding: The combination led to an objective response rate of 81.8% (90% CI 71.1%-89.8%), which increased to 87.3% (90% CI 77.4%-93.9%) with ibrutinib maintenance. At a 25.4-month median follow-up, the median duration of response and progression-free survival were 22.7 (95% CI 12.3-not achieved) and 18.6 (95% CI 12.5-not achieved) months, respectively. The adverse event profile was consistent with the known safety profiles of individual drugs.

Study details: This phase 2 trial included 55 ibrutinib-naive and bortezomib-naive patients with R/R MCL previously treated with ≤2 lines of chemotherapy (of whom 75.6% had ≥1 high-risk features) who received 6 cycles of ibrutinib + bortezomib followed by ibrutinib maintenance.

Disclosures: This study was supported by Janssen and others. Some authors declared serving on the advisory boards of or receiving research funding, consulting fees, honoraria, or meeting or travel support from various sources, including Janssen.

Source: Novak U et al. Combined therapy with ibrutinib and bortezomib followed by ibrutinib maintenance in relapsed or refractory mantle cell lymphoma and high-risk features: A phase 1/2 trial of the European MCL network (SAKK 36/13). EClinicalMedicine. 2023;64:102221 (Sep 21). doi: 10.1016/j.eclinm.2023.102221

Key clinical point: The ibrutinib + bortezomib combination shows durable efficacy and manageable safety in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL), including high-risk patients.

Major finding: The combination led to an objective response rate of 81.8% (90% CI 71.1%-89.8%), which increased to 87.3% (90% CI 77.4%-93.9%) with ibrutinib maintenance. At a 25.4-month median follow-up, the median duration of response and progression-free survival were 22.7 (95% CI 12.3-not achieved) and 18.6 (95% CI 12.5-not achieved) months, respectively. The adverse event profile was consistent with the known safety profiles of individual drugs.

Study details: This phase 2 trial included 55 ibrutinib-naive and bortezomib-naive patients with R/R MCL previously treated with ≤2 lines of chemotherapy (of whom 75.6% had ≥1 high-risk features) who received 6 cycles of ibrutinib + bortezomib followed by ibrutinib maintenance.

Disclosures: This study was supported by Janssen and others. Some authors declared serving on the advisory boards of or receiving research funding, consulting fees, honoraria, or meeting or travel support from various sources, including Janssen.

Source: Novak U et al. Combined therapy with ibrutinib and bortezomib followed by ibrutinib maintenance in relapsed or refractory mantle cell lymphoma and high-risk features: A phase 1/2 trial of the European MCL network (SAKK 36/13). EClinicalMedicine. 2023;64:102221 (Sep 21). doi: 10.1016/j.eclinm.2023.102221