Lymphoma & Plasma Cell Disorders

For patients with multiple myeloma, triplet induction with novel agents beat doublet with regards to early results, according to Lalit Kumar, MD, and colleagues at the All India Institute of Medical sciences Myeloma Group, New Delhi.

The study analyzed 326 multiple myeloma patients who received high-dose, novel agent–based induction therapy prior to autologous stem cell transplant (ASCT) at a single institution, according to a report published in Clinical Lymphoma, Myeloma and Leukemia.

Between January 2005 and December 2018, 326 consecutive patients underwent high-dose chemotherapy and autologous stem cell transplant. The median age of the patients was 52 years; 66% were men, nearly 33% had Revised ISS III disease; almost 16% had high-risk cytogenetics and 23% underwent transplant in second remission after salvage therapy for relapse. A total of 194 patients (59.5%) received induction with two novel agents (thalidomide/dexamethasone, n = 95; lenalidomide/dexamethasone, n = 63; bortezomib/dexamethasone, n = 36) and 132 (40.5%) received three drugs (bortezomib/lenalidomide/dexamethasone, n = 53; bortezomib/liposomal doxorubicin/dexamethasone, n = 42; bortezomib/thalidomide/dexamethasone, n = 31; other n = 3).
 

Outcomes favorable

After transplant 227 (69.8%) patients achieved a complete response; 48 (14.7%) had a very good partial response, 32 (9.8%) had a partial response, and 9 (2.8%) patients had stable disease. Ten (3.1%) patients died of transplant-related complications (before day 100). Triplet induction beat doublet with regards to early response (95.4% vs. 84.02% [doublets], P < .003), stem cell mobilization (88.6% vs. 76.8%, P < .005) and lower day-100 transplant-related mortality (P < .001), However, at a median follow-up of 62.5 months, the median overall response rate (97.5 months triplet vs. 100.0 months doublet) and the median progression free survival (54.5 months vs. 57 months) were not statistically different between the two induction-treatment groups.

Patients who had undergone transplant in a recent period (2016-18) had a better outcome, compared with initial years, which possibly reflects a combined effect of learning curve, use of triplets, and gradual reduction in day-100 mortality, the authors stated.

“Whether newer regimens incorporating monoclonal antibodies (associated with higher [complete response] rate and [minimal residual disease] negativity) would result in further improvement in survival, needs to be determined in future studies,” the researchers concluded.

The authors reported that they had no conflicts.

[email protected]

SOURCE: Kumar L et al. Clin Lymphoma Myeloma Leuk. 2020 Sep 18. doi: 10.1016/j.clml.2020.08.021.

For patients with multiple myeloma, triplet induction with novel agents beat doublet with regards to early results, according to Lalit Kumar, MD, and colleagues at the All India Institute of Medical sciences Myeloma Group, New Delhi.

The study analyzed 326 multiple myeloma patients who received high-dose, novel agent–based induction therapy prior to autologous stem cell transplant (ASCT) at a single institution, according to a report published in Clinical Lymphoma, Myeloma and Leukemia.

Between January 2005 and December 2018, 326 consecutive patients underwent high-dose chemotherapy and autologous stem cell transplant. The median age of the patients was 52 years; 66% were men, nearly 33% had Revised ISS III disease; almost 16% had high-risk cytogenetics and 23% underwent transplant in second remission after salvage therapy for relapse. A total of 194 patients (59.5%) received induction with two novel agents (thalidomide/dexamethasone, n = 95; lenalidomide/dexamethasone, n = 63; bortezomib/dexamethasone, n = 36) and 132 (40.5%) received three drugs (bortezomib/lenalidomide/dexamethasone, n = 53; bortezomib/liposomal doxorubicin/dexamethasone, n = 42; bortezomib/thalidomide/dexamethasone, n = 31; other n = 3).
 

Outcomes favorable

After transplant 227 (69.8%) patients achieved a complete response; 48 (14.7%) had a very good partial response, 32 (9.8%) had a partial response, and 9 (2.8%) patients had stable disease. Ten (3.1%) patients died of transplant-related complications (before day 100). Triplet induction beat doublet with regards to early response (95.4% vs. 84.02% [doublets], P < .003), stem cell mobilization (88.6% vs. 76.8%, P < .005) and lower day-100 transplant-related mortality (P < .001), However, at a median follow-up of 62.5 months, the median overall response rate (97.5 months triplet vs. 100.0 months doublet) and the median progression free survival (54.5 months vs. 57 months) were not statistically different between the two induction-treatment groups.

Patients who had undergone transplant in a recent period (2016-18) had a better outcome, compared with initial years, which possibly reflects a combined effect of learning curve, use of triplets, and gradual reduction in day-100 mortality, the authors stated.

“Whether newer regimens incorporating monoclonal antibodies (associated with higher [complete response] rate and [minimal residual disease] negativity) would result in further improvement in survival, needs to be determined in future studies,” the researchers concluded.

The authors reported that they had no conflicts.

[email protected]

SOURCE: Kumar L et al. Clin Lymphoma Myeloma Leuk. 2020 Sep 18. doi: 10.1016/j.clml.2020.08.021.

For patients with multiple myeloma, triplet induction with novel agents beat doublet with regards to early results, according to Lalit Kumar, MD, and colleagues at the All India Institute of Medical sciences Myeloma Group, New Delhi.

The study analyzed 326 multiple myeloma patients who received high-dose, novel agent–based induction therapy prior to autologous stem cell transplant (ASCT) at a single institution, according to a report published in Clinical Lymphoma, Myeloma and Leukemia.

Between January 2005 and December 2018, 326 consecutive patients underwent high-dose chemotherapy and autologous stem cell transplant. The median age of the patients was 52 years; 66% were men, nearly 33% had Revised ISS III disease; almost 16% had high-risk cytogenetics and 23% underwent transplant in second remission after salvage therapy for relapse. A total of 194 patients (59.5%) received induction with two novel agents (thalidomide/dexamethasone, n = 95; lenalidomide/dexamethasone, n = 63; bortezomib/dexamethasone, n = 36) and 132 (40.5%) received three drugs (bortezomib/lenalidomide/dexamethasone, n = 53; bortezomib/liposomal doxorubicin/dexamethasone, n = 42; bortezomib/thalidomide/dexamethasone, n = 31; other n = 3).
 

Outcomes favorable

After transplant 227 (69.8%) patients achieved a complete response; 48 (14.7%) had a very good partial response, 32 (9.8%) had a partial response, and 9 (2.8%) patients had stable disease. Ten (3.1%) patients died of transplant-related complications (before day 100). Triplet induction beat doublet with regards to early response (95.4% vs. 84.02% [doublets], P < .003), stem cell mobilization (88.6% vs. 76.8%, P < .005) and lower day-100 transplant-related mortality (P < .001), However, at a median follow-up of 62.5 months, the median overall response rate (97.5 months triplet vs. 100.0 months doublet) and the median progression free survival (54.5 months vs. 57 months) were not statistically different between the two induction-treatment groups.

Patients who had undergone transplant in a recent period (2016-18) had a better outcome, compared with initial years, which possibly reflects a combined effect of learning curve, use of triplets, and gradual reduction in day-100 mortality, the authors stated.

“Whether newer regimens incorporating monoclonal antibodies (associated with higher [complete response] rate and [minimal residual disease] negativity) would result in further improvement in survival, needs to be determined in future studies,” the researchers concluded.

The authors reported that they had no conflicts.

[email protected]

SOURCE: Kumar L et al. Clin Lymphoma Myeloma Leuk. 2020 Sep 18. doi: 10.1016/j.clml.2020.08.021.

Two new protein biomarkers may serve as prognostic indicators for outcomes in chronic lymphocytic leukemia (CLL) patients, according to the results of a proteomic assessment of patients’ serum compared to their event-free survival (EFS).

The results were published in Experimental Hematology.

The study attempted to validate the prognostic ability of known proteomic markers measured pretreatment and to search for new proteomic markers that might be related to treatment response in CLL, according to Fatemeh Saberi Hosnijeh, MD, of Erasmus MC, University Medical Center, Rotterdam, The Netherlands, and colleagues.

Baseline serum samples were taken from 51 CLL patients who were then treated with chemoimmunotherapy. The samples were analyzed for 360 proteomic markers, and those results were compared with patient EFS.

Study subjects were selected from patients enrolled in the HOVON 109 clinical trial, a phase 1/2 trial designed to assess the efficacy and safety of first-line therapy involving chlorambucil, rituximab,and lenalidomide in elderly patients and young frail patients with advanced CLL.

The patients assessed comprised 30 men and 21 women, and the median EFS for all patients was 23 months (ranging from 1.25 to 60.9 months).
 

Promising biomarkers

The researchers found that patients who had high serum levels of the proteins sCD23 (P = .026), sCD27 (P = .04), the serine peptidase inhibitor SPINT1 (P = .001), and the surface antigen protein LY9 (P = .0003) had a shorter EFS than those with marker levels below the median.

“Taken together, our results validate the prognostic impact of sCD23 and highlight SPINT1 and LY9 as possible promising markers for treatment response in CLL patients,” the researchers stated.

“Despite the relatively small number of available cases, which had an impact on statistical power, our pilot study identified SPINT1 and LY9 as promising independent prognostic proteomic markers next to sCD23 and sCD27 in patients treated for CLL. Further studies with larger sample sizes are required to validate these results,” the researchers concluded.

This research was supported by a grant from Gilead Sciences and an EU TRANSCAN/Dutch Cancer Society grant. The authors declared that they had no conflicts of interest.

[email protected]

SOURCE: Hosnijeh FS et al. Exp Hematol. 2020;89:55-60.

Two new protein biomarkers may serve as prognostic indicators for outcomes in chronic lymphocytic leukemia (CLL) patients, according to the results of a proteomic assessment of patients’ serum compared to their event-free survival (EFS).

The results were published in Experimental Hematology.

The study attempted to validate the prognostic ability of known proteomic markers measured pretreatment and to search for new proteomic markers that might be related to treatment response in CLL, according to Fatemeh Saberi Hosnijeh, MD, of Erasmus MC, University Medical Center, Rotterdam, The Netherlands, and colleagues.

Baseline serum samples were taken from 51 CLL patients who were then treated with chemoimmunotherapy. The samples were analyzed for 360 proteomic markers, and those results were compared with patient EFS.

Study subjects were selected from patients enrolled in the HOVON 109 clinical trial, a phase 1/2 trial designed to assess the efficacy and safety of first-line therapy involving chlorambucil, rituximab,and lenalidomide in elderly patients and young frail patients with advanced CLL.

The patients assessed comprised 30 men and 21 women, and the median EFS for all patients was 23 months (ranging from 1.25 to 60.9 months).
 

Promising biomarkers

The researchers found that patients who had high serum levels of the proteins sCD23 (P = .026), sCD27 (P = .04), the serine peptidase inhibitor SPINT1 (P = .001), and the surface antigen protein LY9 (P = .0003) had a shorter EFS than those with marker levels below the median.

“Taken together, our results validate the prognostic impact of sCD23 and highlight SPINT1 and LY9 as possible promising markers for treatment response in CLL patients,” the researchers stated.

“Despite the relatively small number of available cases, which had an impact on statistical power, our pilot study identified SPINT1 and LY9 as promising independent prognostic proteomic markers next to sCD23 and sCD27 in patients treated for CLL. Further studies with larger sample sizes are required to validate these results,” the researchers concluded.

This research was supported by a grant from Gilead Sciences and an EU TRANSCAN/Dutch Cancer Society grant. The authors declared that they had no conflicts of interest.

[email protected]

SOURCE: Hosnijeh FS et al. Exp Hematol. 2020;89:55-60.

Two new protein biomarkers may serve as prognostic indicators for outcomes in chronic lymphocytic leukemia (CLL) patients, according to the results of a proteomic assessment of patients’ serum compared to their event-free survival (EFS).

The results were published in Experimental Hematology.

The study attempted to validate the prognostic ability of known proteomic markers measured pretreatment and to search for new proteomic markers that might be related to treatment response in CLL, according to Fatemeh Saberi Hosnijeh, MD, of Erasmus MC, University Medical Center, Rotterdam, The Netherlands, and colleagues.

Baseline serum samples were taken from 51 CLL patients who were then treated with chemoimmunotherapy. The samples were analyzed for 360 proteomic markers, and those results were compared with patient EFS.

Study subjects were selected from patients enrolled in the HOVON 109 clinical trial, a phase 1/2 trial designed to assess the efficacy and safety of first-line therapy involving chlorambucil, rituximab,and lenalidomide in elderly patients and young frail patients with advanced CLL.

The patients assessed comprised 30 men and 21 women, and the median EFS for all patients was 23 months (ranging from 1.25 to 60.9 months).
 

Promising biomarkers

The researchers found that patients who had high serum levels of the proteins sCD23 (P = .026), sCD27 (P = .04), the serine peptidase inhibitor SPINT1 (P = .001), and the surface antigen protein LY9 (P = .0003) had a shorter EFS than those with marker levels below the median.

“Taken together, our results validate the prognostic impact of sCD23 and highlight SPINT1 and LY9 as possible promising markers for treatment response in CLL patients,” the researchers stated.

“Despite the relatively small number of available cases, which had an impact on statistical power, our pilot study identified SPINT1 and LY9 as promising independent prognostic proteomic markers next to sCD23 and sCD27 in patients treated for CLL. Further studies with larger sample sizes are required to validate these results,” the researchers concluded.

This research was supported by a grant from Gilead Sciences and an EU TRANSCAN/Dutch Cancer Society grant. The authors declared that they had no conflicts of interest.

[email protected]

SOURCE: Hosnijeh FS et al. Exp Hematol. 2020;89:55-60.

An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.

The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).

Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.

The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.

The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.

The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).

The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
 

Impact on treatment

The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).

Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).

Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.

On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.

Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.

“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.

“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

Frontline Medical News

Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.

Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.

Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
 

Telehealth, meetings, and trials

The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).

Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).

While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.

Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.

Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.

He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”

This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.

SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.

An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.

The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).

Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.

The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.

The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.

The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).

The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
 

Impact on treatment

The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).

Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).

Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.

On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.

Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.

“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.

“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

Frontline Medical News

Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.

Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.

Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
 

Telehealth, meetings, and trials

The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).

Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).

While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.

Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.

Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.

He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”

This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.

SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.

An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.

The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).

Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.

The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.

The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.

The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).

The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
 

Impact on treatment

The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).

Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).

Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.

On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.

Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.

“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.

“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

Frontline Medical News

Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.

Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.

Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
 

Telehealth, meetings, and trials

The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).

Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).

While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.

Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.

Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.

He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”

This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.

SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.

Although COVID-19 has had negative effects on cancer research, the pandemic has also led to democratization of clinical trials, according to a panelist who spoke at the AACR virtual meeting: COVID-19 and Cancer.

The pandemic has taught researchers how to decentralize trials, which should not only improve patient satisfaction but increase trial accrual by providing access to typically underserved populations, Patricia M. LoRusso, DO, of Yale University, New Haven, Conn., said at the meeting.

Dr. LoRusso was one of six panelists who participated in a forum about changes to cancer trials that were prompted by the pandemic. The forum was moderated by Keith T. Flaherty, MD, of Massachusetts General Hospital in Boston.

Dr. Flaherty asked the panelists to explain adjustments their organizations have made in response to the pandemic, discuss accomplishments, and speculate on future challenges and priorities.
 

Trial, administrative, and patient-care modifications

COVID-19 put some cancer trials on hold. For others, the pandemic forced sponsors and study chairs to reduce trial complexity and identify nonessential aspects of the studies, according to panelist José Baselga, MD, PhD, of AstraZeneca.

Specifically, exploratory objectives were subjugated to patient safety and a focus on the primary endpoints of each trial.

Once the critical data were identified, study chairs were asked to determine whether data could be obtained through technologies that could substitute for face-to-face contact between patients and staff – for example, patient-reported outcome tools and at-home digital monitoring.

Modifications prompted by the pandemic include the following:

• On-site auditing was suspended.
• Oral investigational agents were shipped directly to patients.
• “Remote” informed consent (telephone or video consenting) was permitted.
• Local providers could perform study-related services, with oversight by the research site.
• Minor deviations from the written protocols were allowed, provided the deviations did not affect patient care or data integrity.

“Obviously, the pandemic has been horrible, but what it has allowed us to do, as investigators in the clinical research landscape, … is to change our focus somewhat and realize, first and foremost, the patient is at the center of this,” Dr. LoRusso said.
 

Operational accomplishments and benefits

The pandemic caused a 40% decline in accrual to studies supported by the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) from mid-March to early April, according to James H. Doroshow, MD, of NCI.

However, after modifications to administrative and regulatory procedures, accrual to NCTN trials recovered to approximately 80% of prepandemic levels, Dr. Doroshow said.

The pandemic prompted investigators to leverage tools and technology they had not previously used frequently or at all, the panelists pointed out.

Investigators discovered perforce that telehealth could be used for almost all trial-related assessments. In lieu of physical examination, patients could send pictures of rashes and use electronic devices to monitor blood sugar values and vital signs.

Digital radiographic studies were performed at sites that were most convenient for patients, downloaded, and reinterpreted at the study institution. Visiting nurses and neighborhood laboratories enabled less-frequent in-person visits for assessments.

These adjustments have been particularly important for geographically and/or socioeconomically disadvantaged patients, the panelists said.

Overall, there was agreement among the panelists that shared values and trust among regulatory authorities, sponsors, investigators, and clinicians were impressive in their urgency, sincerity, and patient centricity.

“This pandemic … has forced us to think differently and be nimble and creative to our approach to maintaining our overriding goals while at the same time bringing these innovative therapies forward for patients with cancer and other serious and life-threatening diseases as quickly as possible,” said panelist Kristen M. Hege, MD, of Bristol-Myers Squibb.

In fact, Dr. Hege noted, some cancer-related therapies (e.g., BTK inhibitors, JAK inhibitors, and immunomodulatory agents) were “repurposed” rapidly and tested against COVID-related complications.
 

Streamlining trial regulatory processes

In addition to changing ongoing trials, the pandemic has affected how new research projects are launched.

One new study that came together quickly in response to the pandemic is the NCI COVID-19 in Cancer Patients Study (NCCAPS). NCCAPS is a natural history study with biospecimens and an imaging library. It was approved in just 5 weeks and is active in 650 sites, with “gangbusters” accrual, Dr. Doroshow said.

The rapidness of NCCAPS’ design and implementation should prompt the revision of previously accepted timelines for trial activation and lead to streamlined future processes.

Another project that was launched quickly in response to the pandemic is the COVID-19 evidence accelerator, according to Paul G. Kluetz, MD, of the Food and Drug Administration.

The COVID-19 evidence accelerator integrates real-world evidence into a database to provide investigators and health systems with the ability to gather information, design rapid turnaround queries, and share results. The evidence accelerator can provide study chairs with information that may have relevance to the safety of participants in clinical trials.
 

Future directions and challenges

The panelists agreed that pandemic-related modifications in processes will not only accelerate trial approval and activation but should facilitate higher study accrual, increase the diversity of protocol participants, and decrease the costs associated with clinical trial conduct.

With that in mind, the NCI is planning randomized clinical trials in which “process A” is compared with “process B,” Dr. Doroshow said. The goal is to determine which modifications are most likely to make trials available to patients without compromising data integrity or patient safety.

“How much less data do you need to have an outcome that will be similar?” Dr. Doroshow asked. “How many fewer visits, how many fewer tests, how much can you save? Physicians, clinical trialists, all of us respond to data, and if you get the same outcome at a third of the cost, then everybody benefits.”

Nonetheless, we will need to be vigilant for unintended vulnerabilities from well-intended efforts, according to Dr. Kluetz. Study chairs, sponsors, and regulatory agencies will need to be attentive to whether there are important differences in scan quality or interpretation, missing data that influence trial outcomes, and so on.

Dr. Hege pointed out that differences among data sources may be less important when treatments generate large effects but may be vitally important when the relative differences among treatments are small.

On a practical level, decentralizing clinical research may negatively impact the finances of tertiary care centers, which could threaten the required infrastructure for clinical trials, a few panelists noted.

The relative balance of NCI-, industry-, and investigator-initiated trials may require adjustment so that research income is adequate to maintain the costs associated with cancer clinical trials.
 

Shared goals and democratization

The pandemic has required all stakeholders in clinical research to rely on relationships of trust and shared goals, said Caroline Robert, MD, PhD, of Institut Gustave Roussy in Villejuif, France.

Dr. Kluetz summarized those goals as improving trial efficiencies, decreasing patient burden, decentralizing trials, and maintaining trial integrity.

A decentralized clinical trials operational model could lead to better generalizability of study outcomes, normalization of life for patients on studies, and lower costs of trial conduct. As such, decentralization would promote democratization.

Coupled with ongoing efforts to reduce eligibility criteria in cancer trials, the pandemic has brought operational solutions that should be perpetuated and has reminded us of the interlocking and mutually supportive relationships on which clinical research success depends.

Dr. Doroshow and Dr. Kluetz disclosed no conflicts of interest. All other panelists disclosed financial relationships, including employment, with a range of companies.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Flaherty KT et al. AACR: COVID-19 and Cancer, Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19.

Although COVID-19 has had negative effects on cancer research, the pandemic has also led to democratization of clinical trials, according to a panelist who spoke at the AACR virtual meeting: COVID-19 and Cancer.

The pandemic has taught researchers how to decentralize trials, which should not only improve patient satisfaction but increase trial accrual by providing access to typically underserved populations, Patricia M. LoRusso, DO, of Yale University, New Haven, Conn., said at the meeting.

Dr. LoRusso was one of six panelists who participated in a forum about changes to cancer trials that were prompted by the pandemic. The forum was moderated by Keith T. Flaherty, MD, of Massachusetts General Hospital in Boston.

Dr. Flaherty asked the panelists to explain adjustments their organizations have made in response to the pandemic, discuss accomplishments, and speculate on future challenges and priorities.
 

Trial, administrative, and patient-care modifications

COVID-19 put some cancer trials on hold. For others, the pandemic forced sponsors and study chairs to reduce trial complexity and identify nonessential aspects of the studies, according to panelist José Baselga, MD, PhD, of AstraZeneca.

Specifically, exploratory objectives were subjugated to patient safety and a focus on the primary endpoints of each trial.

Once the critical data were identified, study chairs were asked to determine whether data could be obtained through technologies that could substitute for face-to-face contact between patients and staff – for example, patient-reported outcome tools and at-home digital monitoring.

Modifications prompted by the pandemic include the following:

• On-site auditing was suspended.
• Oral investigational agents were shipped directly to patients.
• “Remote” informed consent (telephone or video consenting) was permitted.
• Local providers could perform study-related services, with oversight by the research site.
• Minor deviations from the written protocols were allowed, provided the deviations did not affect patient care or data integrity.

“Obviously, the pandemic has been horrible, but what it has allowed us to do, as investigators in the clinical research landscape, … is to change our focus somewhat and realize, first and foremost, the patient is at the center of this,” Dr. LoRusso said.
 

Operational accomplishments and benefits

The pandemic caused a 40% decline in accrual to studies supported by the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) from mid-March to early April, according to James H. Doroshow, MD, of NCI.

However, after modifications to administrative and regulatory procedures, accrual to NCTN trials recovered to approximately 80% of prepandemic levels, Dr. Doroshow said.

The pandemic prompted investigators to leverage tools and technology they had not previously used frequently or at all, the panelists pointed out.

Investigators discovered perforce that telehealth could be used for almost all trial-related assessments. In lieu of physical examination, patients could send pictures of rashes and use electronic devices to monitor blood sugar values and vital signs.

Digital radiographic studies were performed at sites that were most convenient for patients, downloaded, and reinterpreted at the study institution. Visiting nurses and neighborhood laboratories enabled less-frequent in-person visits for assessments.

These adjustments have been particularly important for geographically and/or socioeconomically disadvantaged patients, the panelists said.

Overall, there was agreement among the panelists that shared values and trust among regulatory authorities, sponsors, investigators, and clinicians were impressive in their urgency, sincerity, and patient centricity.

“This pandemic … has forced us to think differently and be nimble and creative to our approach to maintaining our overriding goals while at the same time bringing these innovative therapies forward for patients with cancer and other serious and life-threatening diseases as quickly as possible,” said panelist Kristen M. Hege, MD, of Bristol-Myers Squibb.

In fact, Dr. Hege noted, some cancer-related therapies (e.g., BTK inhibitors, JAK inhibitors, and immunomodulatory agents) were “repurposed” rapidly and tested against COVID-related complications.
 

Streamlining trial regulatory processes

In addition to changing ongoing trials, the pandemic has affected how new research projects are launched.

One new study that came together quickly in response to the pandemic is the NCI COVID-19 in Cancer Patients Study (NCCAPS). NCCAPS is a natural history study with biospecimens and an imaging library. It was approved in just 5 weeks and is active in 650 sites, with “gangbusters” accrual, Dr. Doroshow said.

The rapidness of NCCAPS’ design and implementation should prompt the revision of previously accepted timelines for trial activation and lead to streamlined future processes.

Another project that was launched quickly in response to the pandemic is the COVID-19 evidence accelerator, according to Paul G. Kluetz, MD, of the Food and Drug Administration.

The COVID-19 evidence accelerator integrates real-world evidence into a database to provide investigators and health systems with the ability to gather information, design rapid turnaround queries, and share results. The evidence accelerator can provide study chairs with information that may have relevance to the safety of participants in clinical trials.
 

Future directions and challenges

The panelists agreed that pandemic-related modifications in processes will not only accelerate trial approval and activation but should facilitate higher study accrual, increase the diversity of protocol participants, and decrease the costs associated with clinical trial conduct.

With that in mind, the NCI is planning randomized clinical trials in which “process A” is compared with “process B,” Dr. Doroshow said. The goal is to determine which modifications are most likely to make trials available to patients without compromising data integrity or patient safety.

“How much less data do you need to have an outcome that will be similar?” Dr. Doroshow asked. “How many fewer visits, how many fewer tests, how much can you save? Physicians, clinical trialists, all of us respond to data, and if you get the same outcome at a third of the cost, then everybody benefits.”

Nonetheless, we will need to be vigilant for unintended vulnerabilities from well-intended efforts, according to Dr. Kluetz. Study chairs, sponsors, and regulatory agencies will need to be attentive to whether there are important differences in scan quality or interpretation, missing data that influence trial outcomes, and so on.

Dr. Hege pointed out that differences among data sources may be less important when treatments generate large effects but may be vitally important when the relative differences among treatments are small.

On a practical level, decentralizing clinical research may negatively impact the finances of tertiary care centers, which could threaten the required infrastructure for clinical trials, a few panelists noted.

The relative balance of NCI-, industry-, and investigator-initiated trials may require adjustment so that research income is adequate to maintain the costs associated with cancer clinical trials.
 

Shared goals and democratization

The pandemic has required all stakeholders in clinical research to rely on relationships of trust and shared goals, said Caroline Robert, MD, PhD, of Institut Gustave Roussy in Villejuif, France.

Dr. Kluetz summarized those goals as improving trial efficiencies, decreasing patient burden, decentralizing trials, and maintaining trial integrity.

A decentralized clinical trials operational model could lead to better generalizability of study outcomes, normalization of life for patients on studies, and lower costs of trial conduct. As such, decentralization would promote democratization.

Coupled with ongoing efforts to reduce eligibility criteria in cancer trials, the pandemic has brought operational solutions that should be perpetuated and has reminded us of the interlocking and mutually supportive relationships on which clinical research success depends.

Dr. Doroshow and Dr. Kluetz disclosed no conflicts of interest. All other panelists disclosed financial relationships, including employment, with a range of companies.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Flaherty KT et al. AACR: COVID-19 and Cancer, Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19.

Although COVID-19 has had negative effects on cancer research, the pandemic has also led to democratization of clinical trials, according to a panelist who spoke at the AACR virtual meeting: COVID-19 and Cancer.

The pandemic has taught researchers how to decentralize trials, which should not only improve patient satisfaction but increase trial accrual by providing access to typically underserved populations, Patricia M. LoRusso, DO, of Yale University, New Haven, Conn., said at the meeting.

Dr. LoRusso was one of six panelists who participated in a forum about changes to cancer trials that were prompted by the pandemic. The forum was moderated by Keith T. Flaherty, MD, of Massachusetts General Hospital in Boston.

Dr. Flaherty asked the panelists to explain adjustments their organizations have made in response to the pandemic, discuss accomplishments, and speculate on future challenges and priorities.
 

Trial, administrative, and patient-care modifications

COVID-19 put some cancer trials on hold. For others, the pandemic forced sponsors and study chairs to reduce trial complexity and identify nonessential aspects of the studies, according to panelist José Baselga, MD, PhD, of AstraZeneca.

Specifically, exploratory objectives were subjugated to patient safety and a focus on the primary endpoints of each trial.

Once the critical data were identified, study chairs were asked to determine whether data could be obtained through technologies that could substitute for face-to-face contact between patients and staff – for example, patient-reported outcome tools and at-home digital monitoring.

Modifications prompted by the pandemic include the following:

• On-site auditing was suspended.
• Oral investigational agents were shipped directly to patients.
• “Remote” informed consent (telephone or video consenting) was permitted.
• Local providers could perform study-related services, with oversight by the research site.
• Minor deviations from the written protocols were allowed, provided the deviations did not affect patient care or data integrity.

“Obviously, the pandemic has been horrible, but what it has allowed us to do, as investigators in the clinical research landscape, … is to change our focus somewhat and realize, first and foremost, the patient is at the center of this,” Dr. LoRusso said.
 

Operational accomplishments and benefits

The pandemic caused a 40% decline in accrual to studies supported by the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) from mid-March to early April, according to James H. Doroshow, MD, of NCI.

However, after modifications to administrative and regulatory procedures, accrual to NCTN trials recovered to approximately 80% of prepandemic levels, Dr. Doroshow said.

The pandemic prompted investigators to leverage tools and technology they had not previously used frequently or at all, the panelists pointed out.

Investigators discovered perforce that telehealth could be used for almost all trial-related assessments. In lieu of physical examination, patients could send pictures of rashes and use electronic devices to monitor blood sugar values and vital signs.

Digital radiographic studies were performed at sites that were most convenient for patients, downloaded, and reinterpreted at the study institution. Visiting nurses and neighborhood laboratories enabled less-frequent in-person visits for assessments.

These adjustments have been particularly important for geographically and/or socioeconomically disadvantaged patients, the panelists said.

Overall, there was agreement among the panelists that shared values and trust among regulatory authorities, sponsors, investigators, and clinicians were impressive in their urgency, sincerity, and patient centricity.

“This pandemic … has forced us to think differently and be nimble and creative to our approach to maintaining our overriding goals while at the same time bringing these innovative therapies forward for patients with cancer and other serious and life-threatening diseases as quickly as possible,” said panelist Kristen M. Hege, MD, of Bristol-Myers Squibb.

In fact, Dr. Hege noted, some cancer-related therapies (e.g., BTK inhibitors, JAK inhibitors, and immunomodulatory agents) were “repurposed” rapidly and tested against COVID-related complications.
 

Streamlining trial regulatory processes

In addition to changing ongoing trials, the pandemic has affected how new research projects are launched.

One new study that came together quickly in response to the pandemic is the NCI COVID-19 in Cancer Patients Study (NCCAPS). NCCAPS is a natural history study with biospecimens and an imaging library. It was approved in just 5 weeks and is active in 650 sites, with “gangbusters” accrual, Dr. Doroshow said.

The rapidness of NCCAPS’ design and implementation should prompt the revision of previously accepted timelines for trial activation and lead to streamlined future processes.

Another project that was launched quickly in response to the pandemic is the COVID-19 evidence accelerator, according to Paul G. Kluetz, MD, of the Food and Drug Administration.

The COVID-19 evidence accelerator integrates real-world evidence into a database to provide investigators and health systems with the ability to gather information, design rapid turnaround queries, and share results. The evidence accelerator can provide study chairs with information that may have relevance to the safety of participants in clinical trials.
 

Future directions and challenges

The panelists agreed that pandemic-related modifications in processes will not only accelerate trial approval and activation but should facilitate higher study accrual, increase the diversity of protocol participants, and decrease the costs associated with clinical trial conduct.

With that in mind, the NCI is planning randomized clinical trials in which “process A” is compared with “process B,” Dr. Doroshow said. The goal is to determine which modifications are most likely to make trials available to patients without compromising data integrity or patient safety.

“How much less data do you need to have an outcome that will be similar?” Dr. Doroshow asked. “How many fewer visits, how many fewer tests, how much can you save? Physicians, clinical trialists, all of us respond to data, and if you get the same outcome at a third of the cost, then everybody benefits.”

Nonetheless, we will need to be vigilant for unintended vulnerabilities from well-intended efforts, according to Dr. Kluetz. Study chairs, sponsors, and regulatory agencies will need to be attentive to whether there are important differences in scan quality or interpretation, missing data that influence trial outcomes, and so on.

Dr. Hege pointed out that differences among data sources may be less important when treatments generate large effects but may be vitally important when the relative differences among treatments are small.

On a practical level, decentralizing clinical research may negatively impact the finances of tertiary care centers, which could threaten the required infrastructure for clinical trials, a few panelists noted.

The relative balance of NCI-, industry-, and investigator-initiated trials may require adjustment so that research income is adequate to maintain the costs associated with cancer clinical trials.
 

Shared goals and democratization

The pandemic has required all stakeholders in clinical research to rely on relationships of trust and shared goals, said Caroline Robert, MD, PhD, of Institut Gustave Roussy in Villejuif, France.

Dr. Kluetz summarized those goals as improving trial efficiencies, decreasing patient burden, decentralizing trials, and maintaining trial integrity.

A decentralized clinical trials operational model could lead to better generalizability of study outcomes, normalization of life for patients on studies, and lower costs of trial conduct. As such, decentralization would promote democratization.

Coupled with ongoing efforts to reduce eligibility criteria in cancer trials, the pandemic has brought operational solutions that should be perpetuated and has reminded us of the interlocking and mutually supportive relationships on which clinical research success depends.

Dr. Doroshow and Dr. Kluetz disclosed no conflicts of interest. All other panelists disclosed financial relationships, including employment, with a range of companies.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Flaherty KT et al. AACR: COVID-19 and Cancer, Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19.

Statin use was associated with an overall reduction of the risk of death in multiple myeloma (MM) patients, according to a report published in Clinical Lymphoma, Myeloma & Leukemia.

Statins maintained their benefit in patients with multiple myeloma treated with modern-day chemotherapy regimens based on novel agents, but the benefit is less pronounced, reported Amber Afzal, MD, Washington University, St Louis, and colleagues.

Dr. Afzal and colleagues assessed results from 5,922 patients who were diagnosed with multiple myeloma within the study period between 2007 and 2013. The association of statins with mortality in patients with MM was determined using multivariate Cox proportional hazards regression analysis, and a subanalysis was also performed to investigate the effect of statins on mortality in those patients treated with novel agents.
 

Mortality reduction seen

The study found that the use of statins was associated with a 21% reduction in risk of death (adjusted hazard ratio,] 0.79; 95% confidence interval, 0.74-0.84) among all patients with MM. Among the patents treated with novel agents (n = 3,603), statins reduced mortality by 10% (aHR, 0.90; 95% CI, 0.83-0.98).

“Our current study is the first one to support the survival benefit of statins in patients with myeloma treated with modern-day regimens based on novel agents, although it appears the benefit may not be as pronounced. Therefore, as myeloma regimens become more effective, the benefits of statins may diminish,” the researchers concluded.

The authors reported that they had no relevant disclosures.

[email protected]

SOURCE: Afzal A et al. Clin Lymphoma Myeloma Leuk. 2020 Jul 16. doi: 10.1016/j.clml.2020.07.003.

Statin use was associated with an overall reduction of the risk of death in multiple myeloma (MM) patients, according to a report published in Clinical Lymphoma, Myeloma & Leukemia.

Statins maintained their benefit in patients with multiple myeloma treated with modern-day chemotherapy regimens based on novel agents, but the benefit is less pronounced, reported Amber Afzal, MD, Washington University, St Louis, and colleagues.

Dr. Afzal and colleagues assessed results from 5,922 patients who were diagnosed with multiple myeloma within the study period between 2007 and 2013. The association of statins with mortality in patients with MM was determined using multivariate Cox proportional hazards regression analysis, and a subanalysis was also performed to investigate the effect of statins on mortality in those patients treated with novel agents.
 

Mortality reduction seen

The study found that the use of statins was associated with a 21% reduction in risk of death (adjusted hazard ratio,] 0.79; 95% confidence interval, 0.74-0.84) among all patients with MM. Among the patents treated with novel agents (n = 3,603), statins reduced mortality by 10% (aHR, 0.90; 95% CI, 0.83-0.98).

“Our current study is the first one to support the survival benefit of statins in patients with myeloma treated with modern-day regimens based on novel agents, although it appears the benefit may not be as pronounced. Therefore, as myeloma regimens become more effective, the benefits of statins may diminish,” the researchers concluded.

The authors reported that they had no relevant disclosures.

[email protected]

SOURCE: Afzal A et al. Clin Lymphoma Myeloma Leuk. 2020 Jul 16. doi: 10.1016/j.clml.2020.07.003.

Statin use was associated with an overall reduction of the risk of death in multiple myeloma (MM) patients, according to a report published in Clinical Lymphoma, Myeloma & Leukemia.

Statins maintained their benefit in patients with multiple myeloma treated with modern-day chemotherapy regimens based on novel agents, but the benefit is less pronounced, reported Amber Afzal, MD, Washington University, St Louis, and colleagues.

Dr. Afzal and colleagues assessed results from 5,922 patients who were diagnosed with multiple myeloma within the study period between 2007 and 2013. The association of statins with mortality in patients with MM was determined using multivariate Cox proportional hazards regression analysis, and a subanalysis was also performed to investigate the effect of statins on mortality in those patients treated with novel agents.
 

Mortality reduction seen

The study found that the use of statins was associated with a 21% reduction in risk of death (adjusted hazard ratio,] 0.79; 95% confidence interval, 0.74-0.84) among all patients with MM. Among the patents treated with novel agents (n = 3,603), statins reduced mortality by 10% (aHR, 0.90; 95% CI, 0.83-0.98).

“Our current study is the first one to support the survival benefit of statins in patients with myeloma treated with modern-day regimens based on novel agents, although it appears the benefit may not be as pronounced. Therefore, as myeloma regimens become more effective, the benefits of statins may diminish,” the researchers concluded.

The authors reported that they had no relevant disclosures.

[email protected]

SOURCE: Afzal A et al. Clin Lymphoma Myeloma Leuk. 2020 Jul 16. doi: 10.1016/j.clml.2020.07.003.

The largest study of its kind has found no positive association between personal use of permanent hair dye and the risk for most cancers and cancer mortality.

The findings come from the Nurses’ Health Study, an ongoing prospective cohort study of more than 117,000 women who have been followed for 36 years and who did not have cancer at baseline.

The findings were published online on September 2 in the BMJ.

The results “offer some reassurance against concerns that personal use of permanent hair dyes might be associated with increased cancer risk or mortality,” write the investigators, with first author Yin Zhang, PhD, of Harvard Medical School, Boston.

The findings, which are limited to White women in the United States, indicate correlation, not causation, the authors emphasize.

Nevertheless, the researchers found an increased risk for some cancers among hair dye users, especially with greater cumulative dose (200 or more uses during the study period). The risk was increased for basal cell carcinoma, breast cancer (specifically, estrogen receptor negative [ER–], progesterone receptor negative [PR–], and hormone receptor negative [ER–, PR–]), and ovarian cancer.

A British expert not involved in the study dismissed these findings. “The reported associations are very weak, and, given the number of associations reported in this manuscript, they are very likely to be chance findings,” commented Paul Pharoah, PhD, professor of cancer epidemiology at the University of Cambridge (England).

“For the cancers where an increase in risk is reported, the results are not compelling. Even if they were real findings, the associations may not be cause-and-effect, and, even if they were causal associations, the magnitude of the effects are so small that any risk would be trivial.

“In short, none of the findings reported in this manuscript suggest that women who use hair dye are putting themselves at increased risk of cancer,” he stated.

A U.S. researcher who has previously coauthored a study suggesting an association between hair dye and breast cancer agreed that the increases in risk reported in this current study are “small.” But they are “of interest,” especially for breast and ovarian cancer, said Alexandra White, PhD, of the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.

Hair dyes include compounds that “are not just potential carcinogens but also act as endocrine disruptors,” she said in an interview.

“In both breast and ovarian cancer, we know that hormones play an important part in the etiology ... so it’s biologically plausible that you would see [these associations in the current study],” added Dr. White, who was approached for comment.

However, she added that, even with the “modest” 20%-28% increase in the relative risk for certain breast cancers linked to a heavy cumulative dose of dyes in the current study, “there doesn’t seem to be any strong association with any cancer type.”

But she also pointed out that the most outstanding risk association was among ER–/PR– breast cancers, which are the “most aggressive and difficult to treat,” and thus the new findings are “important.”

Dr. White is the lead author of a 2019 study that received a lot of media attention because it rang an alarm bell about hair dyes and breast cancer risk.

That study concluded that ever using permanent hair dye or hair straighteners was associated with a higher risk for breast cancer than never using them and that this higher risk was especially associated with Black women. However, the study participants were from the prospective Sister Study. The participants in that study had no history of breast cancer, but they each had at least one sister who did. This family history of breast cancer may represent selection bias.
 

With changes in the 1980s, even safer now?

The study of hair dyes and cancer has “major public health implications” because the use of hair dye is widespread, Dr. Zhang and colleagues write in their article. They estimate that 50% to 80% of women and 10% of men aged 40 years and older in the United States and Europe use hair dye.

Permanent hair dyes “pose the greatest potential concern,” they stated, adding that these account for approximately 80% of hair dyes used in the United States and Europe and an even higher percentage in Asia.

The International Agency for Research on Cancer classifies occupational exposure to hair dyes as probably carcinogenic, but the carcinogenicity resulting from personal use of hair dyes is not classifiable – thus, there is no warning about at-home usage.

Notably, there was “a huge and very important” change in hair dye ingredients in the 1980s after the Food and Drug Administration warned about some chemicals in permanent hair dyes and the cosmetic industry altered their formulas, lead author Dr. Zhang said.

However, the researchers could not analyze use before and after the changes because not enough women reported first use of permanent hair dye after 1980 (only 1890 of 117,200 participants).

“We could expect that the current ingredients should make it safer,” Dr. Zhang said.
 

Study details

The researchers report that ever-users of permanent hair dyes had no significant increases in risk for solid cancers (n = 20,805; hazard ratio, 0.98, 95% confidence interval, 0.96-1.01) or hematopoietic cancers overall (n = 1,807; HR, 1.00; 95% CI, 0.91-1.10) compared with nonusers.

Additionally, ever-users did not have an increased risk for most specific cancers or cancer-related death (n = 4,860; HR, 0.96; 95% CI, 0.91-1.02).

As noted above, there were some exceptions.

Basal cell carcinoma risk was slightly increased for ever-users (n = 22,560; HR, 1.05; 95% CI, 1.02-1.08). Cumulative dose (a calculation of duration and frequency) was positively associated with risk for ER– breast cancer, PR– breast cancer, ER–/PR– breast cancer, and ovarian cancer, with risk rising in accordance with the total amount of dye.

Notably, at a cumulative dose of ≥200 uses, there was a 20% increase in the relative risk for ER- breast cancer (n = 1521; HR, 1.20; 95% CI, 1.02-1.41; P value for trend, .03). At the same cumulative dose, there was a 28% increase in the relative risk for ER-/PR- breast cancer (n = 1287; HR, 1.28, 95% CI, 1.08-1.52; P value for trend, .006).

In addition, an increased risk for Hodgkin lymphoma was observed, but only for women with naturally dark hair (the calculation was based on 70 women, 24 of whom had dark hair).

In a press statement, senior author Eva Schernhammer, PhD, of Harvard and the Medical University of Vienna, said the results “justify further prospective validation.”

She also explained that there are many variables to consider in this research, including different populations and countries, different susceptibility genotypes, different exposure settings (personal use vs. occupational exposure), and different colors of the permanent hair dyes used (dark dyes vs. light dyes).

Geographic location is a particularly important variable, suggested the study authors.

They pointed out that Europe, but not the United States, banned some individual hair dye ingredients that were considered carcinogenic during both the 1980s and 2000s. One country has even tighter oversight: “The most restrictive regulation of hair dyes exists in Japan, where cosmetic products are considered equivalent to drugs.”

The study was funded by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The study authors and Dr. White have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The largest study of its kind has found no positive association between personal use of permanent hair dye and the risk for most cancers and cancer mortality.

The findings come from the Nurses’ Health Study, an ongoing prospective cohort study of more than 117,000 women who have been followed for 36 years and who did not have cancer at baseline.

The findings were published online on September 2 in the BMJ.

The results “offer some reassurance against concerns that personal use of permanent hair dyes might be associated with increased cancer risk or mortality,” write the investigators, with first author Yin Zhang, PhD, of Harvard Medical School, Boston.

The findings, which are limited to White women in the United States, indicate correlation, not causation, the authors emphasize.

Nevertheless, the researchers found an increased risk for some cancers among hair dye users, especially with greater cumulative dose (200 or more uses during the study period). The risk was increased for basal cell carcinoma, breast cancer (specifically, estrogen receptor negative [ER–], progesterone receptor negative [PR–], and hormone receptor negative [ER–, PR–]), and ovarian cancer.

A British expert not involved in the study dismissed these findings. “The reported associations are very weak, and, given the number of associations reported in this manuscript, they are very likely to be chance findings,” commented Paul Pharoah, PhD, professor of cancer epidemiology at the University of Cambridge (England).

“For the cancers where an increase in risk is reported, the results are not compelling. Even if they were real findings, the associations may not be cause-and-effect, and, even if they were causal associations, the magnitude of the effects are so small that any risk would be trivial.

“In short, none of the findings reported in this manuscript suggest that women who use hair dye are putting themselves at increased risk of cancer,” he stated.

A U.S. researcher who has previously coauthored a study suggesting an association between hair dye and breast cancer agreed that the increases in risk reported in this current study are “small.” But they are “of interest,” especially for breast and ovarian cancer, said Alexandra White, PhD, of the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.

Hair dyes include compounds that “are not just potential carcinogens but also act as endocrine disruptors,” she said in an interview.

“In both breast and ovarian cancer, we know that hormones play an important part in the etiology ... so it’s biologically plausible that you would see [these associations in the current study],” added Dr. White, who was approached for comment.

However, she added that, even with the “modest” 20%-28% increase in the relative risk for certain breast cancers linked to a heavy cumulative dose of dyes in the current study, “there doesn’t seem to be any strong association with any cancer type.”

But she also pointed out that the most outstanding risk association was among ER–/PR– breast cancers, which are the “most aggressive and difficult to treat,” and thus the new findings are “important.”

Dr. White is the lead author of a 2019 study that received a lot of media attention because it rang an alarm bell about hair dyes and breast cancer risk.

That study concluded that ever using permanent hair dye or hair straighteners was associated with a higher risk for breast cancer than never using them and that this higher risk was especially associated with Black women. However, the study participants were from the prospective Sister Study. The participants in that study had no history of breast cancer, but they each had at least one sister who did. This family history of breast cancer may represent selection bias.
 

With changes in the 1980s, even safer now?

The study of hair dyes and cancer has “major public health implications” because the use of hair dye is widespread, Dr. Zhang and colleagues write in their article. They estimate that 50% to 80% of women and 10% of men aged 40 years and older in the United States and Europe use hair dye.

Permanent hair dyes “pose the greatest potential concern,” they stated, adding that these account for approximately 80% of hair dyes used in the United States and Europe and an even higher percentage in Asia.

The International Agency for Research on Cancer classifies occupational exposure to hair dyes as probably carcinogenic, but the carcinogenicity resulting from personal use of hair dyes is not classifiable – thus, there is no warning about at-home usage.

Notably, there was “a huge and very important” change in hair dye ingredients in the 1980s after the Food and Drug Administration warned about some chemicals in permanent hair dyes and the cosmetic industry altered their formulas, lead author Dr. Zhang said.

However, the researchers could not analyze use before and after the changes because not enough women reported first use of permanent hair dye after 1980 (only 1890 of 117,200 participants).

“We could expect that the current ingredients should make it safer,” Dr. Zhang said.
 

Study details

The researchers report that ever-users of permanent hair dyes had no significant increases in risk for solid cancers (n = 20,805; hazard ratio, 0.98, 95% confidence interval, 0.96-1.01) or hematopoietic cancers overall (n = 1,807; HR, 1.00; 95% CI, 0.91-1.10) compared with nonusers.

Additionally, ever-users did not have an increased risk for most specific cancers or cancer-related death (n = 4,860; HR, 0.96; 95% CI, 0.91-1.02).

As noted above, there were some exceptions.

Basal cell carcinoma risk was slightly increased for ever-users (n = 22,560; HR, 1.05; 95% CI, 1.02-1.08). Cumulative dose (a calculation of duration and frequency) was positively associated with risk for ER– breast cancer, PR– breast cancer, ER–/PR– breast cancer, and ovarian cancer, with risk rising in accordance with the total amount of dye.

Notably, at a cumulative dose of ≥200 uses, there was a 20% increase in the relative risk for ER- breast cancer (n = 1521; HR, 1.20; 95% CI, 1.02-1.41; P value for trend, .03). At the same cumulative dose, there was a 28% increase in the relative risk for ER-/PR- breast cancer (n = 1287; HR, 1.28, 95% CI, 1.08-1.52; P value for trend, .006).

In addition, an increased risk for Hodgkin lymphoma was observed, but only for women with naturally dark hair (the calculation was based on 70 women, 24 of whom had dark hair).

In a press statement, senior author Eva Schernhammer, PhD, of Harvard and the Medical University of Vienna, said the results “justify further prospective validation.”

She also explained that there are many variables to consider in this research, including different populations and countries, different susceptibility genotypes, different exposure settings (personal use vs. occupational exposure), and different colors of the permanent hair dyes used (dark dyes vs. light dyes).

Geographic location is a particularly important variable, suggested the study authors.

They pointed out that Europe, but not the United States, banned some individual hair dye ingredients that were considered carcinogenic during both the 1980s and 2000s. One country has even tighter oversight: “The most restrictive regulation of hair dyes exists in Japan, where cosmetic products are considered equivalent to drugs.”

The study was funded by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The study authors and Dr. White have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The largest study of its kind has found no positive association between personal use of permanent hair dye and the risk for most cancers and cancer mortality.

The findings come from the Nurses’ Health Study, an ongoing prospective cohort study of more than 117,000 women who have been followed for 36 years and who did not have cancer at baseline.

The findings were published online on September 2 in the BMJ.

The results “offer some reassurance against concerns that personal use of permanent hair dyes might be associated with increased cancer risk or mortality,” write the investigators, with first author Yin Zhang, PhD, of Harvard Medical School, Boston.

The findings, which are limited to White women in the United States, indicate correlation, not causation, the authors emphasize.

Nevertheless, the researchers found an increased risk for some cancers among hair dye users, especially with greater cumulative dose (200 or more uses during the study period). The risk was increased for basal cell carcinoma, breast cancer (specifically, estrogen receptor negative [ER–], progesterone receptor negative [PR–], and hormone receptor negative [ER–, PR–]), and ovarian cancer.

A British expert not involved in the study dismissed these findings. “The reported associations are very weak, and, given the number of associations reported in this manuscript, they are very likely to be chance findings,” commented Paul Pharoah, PhD, professor of cancer epidemiology at the University of Cambridge (England).

“For the cancers where an increase in risk is reported, the results are not compelling. Even if they were real findings, the associations may not be cause-and-effect, and, even if they were causal associations, the magnitude of the effects are so small that any risk would be trivial.

“In short, none of the findings reported in this manuscript suggest that women who use hair dye are putting themselves at increased risk of cancer,” he stated.

A U.S. researcher who has previously coauthored a study suggesting an association between hair dye and breast cancer agreed that the increases in risk reported in this current study are “small.” But they are “of interest,” especially for breast and ovarian cancer, said Alexandra White, PhD, of the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.

Hair dyes include compounds that “are not just potential carcinogens but also act as endocrine disruptors,” she said in an interview.

“In both breast and ovarian cancer, we know that hormones play an important part in the etiology ... so it’s biologically plausible that you would see [these associations in the current study],” added Dr. White, who was approached for comment.

However, she added that, even with the “modest” 20%-28% increase in the relative risk for certain breast cancers linked to a heavy cumulative dose of dyes in the current study, “there doesn’t seem to be any strong association with any cancer type.”

But she also pointed out that the most outstanding risk association was among ER–/PR– breast cancers, which are the “most aggressive and difficult to treat,” and thus the new findings are “important.”

Dr. White is the lead author of a 2019 study that received a lot of media attention because it rang an alarm bell about hair dyes and breast cancer risk.

That study concluded that ever using permanent hair dye or hair straighteners was associated with a higher risk for breast cancer than never using them and that this higher risk was especially associated with Black women. However, the study participants were from the prospective Sister Study. The participants in that study had no history of breast cancer, but they each had at least one sister who did. This family history of breast cancer may represent selection bias.
 

With changes in the 1980s, even safer now?

The study of hair dyes and cancer has “major public health implications” because the use of hair dye is widespread, Dr. Zhang and colleagues write in their article. They estimate that 50% to 80% of women and 10% of men aged 40 years and older in the United States and Europe use hair dye.

Permanent hair dyes “pose the greatest potential concern,” they stated, adding that these account for approximately 80% of hair dyes used in the United States and Europe and an even higher percentage in Asia.

The International Agency for Research on Cancer classifies occupational exposure to hair dyes as probably carcinogenic, but the carcinogenicity resulting from personal use of hair dyes is not classifiable – thus, there is no warning about at-home usage.

Notably, there was “a huge and very important” change in hair dye ingredients in the 1980s after the Food and Drug Administration warned about some chemicals in permanent hair dyes and the cosmetic industry altered their formulas, lead author Dr. Zhang said.

However, the researchers could not analyze use before and after the changes because not enough women reported first use of permanent hair dye after 1980 (only 1890 of 117,200 participants).

“We could expect that the current ingredients should make it safer,” Dr. Zhang said.
 

Study details

The researchers report that ever-users of permanent hair dyes had no significant increases in risk for solid cancers (n = 20,805; hazard ratio, 0.98, 95% confidence interval, 0.96-1.01) or hematopoietic cancers overall (n = 1,807; HR, 1.00; 95% CI, 0.91-1.10) compared with nonusers.

Additionally, ever-users did not have an increased risk for most specific cancers or cancer-related death (n = 4,860; HR, 0.96; 95% CI, 0.91-1.02).

As noted above, there were some exceptions.

Basal cell carcinoma risk was slightly increased for ever-users (n = 22,560; HR, 1.05; 95% CI, 1.02-1.08). Cumulative dose (a calculation of duration and frequency) was positively associated with risk for ER– breast cancer, PR– breast cancer, ER–/PR– breast cancer, and ovarian cancer, with risk rising in accordance with the total amount of dye.

Notably, at a cumulative dose of ≥200 uses, there was a 20% increase in the relative risk for ER- breast cancer (n = 1521; HR, 1.20; 95% CI, 1.02-1.41; P value for trend, .03). At the same cumulative dose, there was a 28% increase in the relative risk for ER-/PR- breast cancer (n = 1287; HR, 1.28, 95% CI, 1.08-1.52; P value for trend, .006).

In addition, an increased risk for Hodgkin lymphoma was observed, but only for women with naturally dark hair (the calculation was based on 70 women, 24 of whom had dark hair).

In a press statement, senior author Eva Schernhammer, PhD, of Harvard and the Medical University of Vienna, said the results “justify further prospective validation.”

She also explained that there are many variables to consider in this research, including different populations and countries, different susceptibility genotypes, different exposure settings (personal use vs. occupational exposure), and different colors of the permanent hair dyes used (dark dyes vs. light dyes).

Geographic location is a particularly important variable, suggested the study authors.

They pointed out that Europe, but not the United States, banned some individual hair dye ingredients that were considered carcinogenic during both the 1980s and 2000s. One country has even tighter oversight: “The most restrictive regulation of hair dyes exists in Japan, where cosmetic products are considered equivalent to drugs.”

The study was funded by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The study authors and Dr. White have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The STAT3 pathway is important to the development of many cancers, but so far, no Food and Drug Administration–approved drugs are ready for clinical use. Napabucasin, a novel oral small-molecule inhibitor of signal transducer and activator of transcription 3 (STAT3), blocks tumor growth and resists metastasis in a broad spectrum of solid tumors. Napabucasin was now found to be effective in inhibiting diffuse large beta cell lymphoma (DLBCL) in cell lines and in in vitro testing, as reported by Xue Li of the West China Hospital, Sichuan (China) University, and colleagues.

In addition, the effects of napabucasin were found to be synergistic with the use of doxorubicin, a standard DLBCL therapy agent, according to the report, published online in Cancer Letters.
 

‘Dramatic’ results

The researchers found that 34% (23/69) of DLBCL patients expressed STAT3 in tumor tissues. When they tested napabucasin in a variety of DLBCL cell lines they found that the drug exhibited potent cytotoxicity in a dose-dependent manner. In addition, they found that napabucasin induced intrinsic and extrinsic cell apoptosis, downregulated the expression of STAT3 target genes, including the antiapoptotic protein Mcl-1, and regulated the mitogen-activated protein kinase (MAPK) pathway, all important indicators of antitumor effectiveness in vitro.

In cells treated with napabucasin and doxorubicin alone and in combination, napabucasin alone significantly suppressed tumor growth, compared with that of the control (P < .01), achieving tumor growth inhibition (TGI) of 78.8%. The combination treatment, “with a dramatic TGI of 98.2%,” was more effective than doxorubicin monotherapy (TGI = 63.2%; P < .05), according to the researchers.

“Our study provided evidence that napabucasin is an attractive candidate drug either as a monotherapy or in combination therapies for DLBCL treatment. Further work studying the clinical efficacy and combination treatment schedule should be performed for personalized therapy,” the researchers concluded.

The work was supported by grants from the Chinese government. The authors stated that they had no conflicts of interest.

[email protected]

SOURCE: Li X et al. Cancer Lett. 2020 Aug 14. doi: 10.1016/j.canlet.2020.07.032.

The STAT3 pathway is important to the development of many cancers, but so far, no Food and Drug Administration–approved drugs are ready for clinical use. Napabucasin, a novel oral small-molecule inhibitor of signal transducer and activator of transcription 3 (STAT3), blocks tumor growth and resists metastasis in a broad spectrum of solid tumors. Napabucasin was now found to be effective in inhibiting diffuse large beta cell lymphoma (DLBCL) in cell lines and in in vitro testing, as reported by Xue Li of the West China Hospital, Sichuan (China) University, and colleagues.

In addition, the effects of napabucasin were found to be synergistic with the use of doxorubicin, a standard DLBCL therapy agent, according to the report, published online in Cancer Letters.
 

‘Dramatic’ results

The researchers found that 34% (23/69) of DLBCL patients expressed STAT3 in tumor tissues. When they tested napabucasin in a variety of DLBCL cell lines they found that the drug exhibited potent cytotoxicity in a dose-dependent manner. In addition, they found that napabucasin induced intrinsic and extrinsic cell apoptosis, downregulated the expression of STAT3 target genes, including the antiapoptotic protein Mcl-1, and regulated the mitogen-activated protein kinase (MAPK) pathway, all important indicators of antitumor effectiveness in vitro.

In cells treated with napabucasin and doxorubicin alone and in combination, napabucasin alone significantly suppressed tumor growth, compared with that of the control (P < .01), achieving tumor growth inhibition (TGI) of 78.8%. The combination treatment, “with a dramatic TGI of 98.2%,” was more effective than doxorubicin monotherapy (TGI = 63.2%; P < .05), according to the researchers.

“Our study provided evidence that napabucasin is an attractive candidate drug either as a monotherapy or in combination therapies for DLBCL treatment. Further work studying the clinical efficacy and combination treatment schedule should be performed for personalized therapy,” the researchers concluded.

The work was supported by grants from the Chinese government. The authors stated that they had no conflicts of interest.

[email protected]

SOURCE: Li X et al. Cancer Lett. 2020 Aug 14. doi: 10.1016/j.canlet.2020.07.032.

The STAT3 pathway is important to the development of many cancers, but so far, no Food and Drug Administration–approved drugs are ready for clinical use. Napabucasin, a novel oral small-molecule inhibitor of signal transducer and activator of transcription 3 (STAT3), blocks tumor growth and resists metastasis in a broad spectrum of solid tumors. Napabucasin was now found to be effective in inhibiting diffuse large beta cell lymphoma (DLBCL) in cell lines and in in vitro testing, as reported by Xue Li of the West China Hospital, Sichuan (China) University, and colleagues.

In addition, the effects of napabucasin were found to be synergistic with the use of doxorubicin, a standard DLBCL therapy agent, according to the report, published online in Cancer Letters.
 

‘Dramatic’ results

The researchers found that 34% (23/69) of DLBCL patients expressed STAT3 in tumor tissues. When they tested napabucasin in a variety of DLBCL cell lines they found that the drug exhibited potent cytotoxicity in a dose-dependent manner. In addition, they found that napabucasin induced intrinsic and extrinsic cell apoptosis, downregulated the expression of STAT3 target genes, including the antiapoptotic protein Mcl-1, and regulated the mitogen-activated protein kinase (MAPK) pathway, all important indicators of antitumor effectiveness in vitro.

In cells treated with napabucasin and doxorubicin alone and in combination, napabucasin alone significantly suppressed tumor growth, compared with that of the control (P < .01), achieving tumor growth inhibition (TGI) of 78.8%. The combination treatment, “with a dramatic TGI of 98.2%,” was more effective than doxorubicin monotherapy (TGI = 63.2%; P < .05), according to the researchers.

“Our study provided evidence that napabucasin is an attractive candidate drug either as a monotherapy or in combination therapies for DLBCL treatment. Further work studying the clinical efficacy and combination treatment schedule should be performed for personalized therapy,” the researchers concluded.

The work was supported by grants from the Chinese government. The authors stated that they had no conflicts of interest.

[email protected]

SOURCE: Li X et al. Cancer Lett. 2020 Aug 14. doi: 10.1016/j.canlet.2020.07.032.