User login
CAR T-cell studies to be presented at ASH
Several studies set to be presented at the 2018 ASH Annual Meeting provide new insights regarding chimeric antigen receptor (CAR) T-cell therapies.
One study suggests ibrutinib may enhance CAR T-cell therapy in patients with chronic lymphocytic leukemia (CLL), and another suggests checkpoint inhibitors can augment CAR T-cell therapy in certain patients with B-cell acute lymphoblastic leukemia (ALL).
Two additional studies indicate that responses to tisagenlecleucel are durable in both ALL and diffuse large B-cell lymphoma (DLBCL).
A fifth study suggests hematopoietic stem cell transplant (HSCT) may reduce the risk of relapse after CAR T-cell therapy.
ASH Secretary Robert A. Brodsky, MD, of Johns Hopkins University in Baltimore, Maryland, discussed these studies during a media briefing ahead of the ASH Annual Meeting.
Ibrutinib
In the ibrutinib study (abstract 299), patients received the BTK inhibitor starting 2 weeks prior to leukapheresis and continued until 3 months after treatment with JCAR014.
Data suggest this strategy may improve responses and decrease the incidence of severe cytokine release syndrome in patients with relapsed or refractory CLL.
Responses occurred in 88% of patients who received ibrutinib and 56% of those who did not.
Grade 3-5 cytokine release syndrome occurred in 5 of 19 patients (26%) in the no-ibrutinib cohort and 0 of 17 patients in the ibrutinib cohort.
These findings are “early and preliminary but very exciting” Dr. Brodsky said.
Checkpoint inhibitors
Early results of the checkpoint inhibitor study (abstract 556) suggest that pembrolizumab or nivolumab may augment CD19-directed CAR T-cell therapy.
The 14 patients studied had early CAR T-cell loss, partial response, or no response to CAR T-cell therapy. Thirteen patients had B-cell ALL, and one had B lymphoblastic lymphoma.
CD19-directed CAR T-cell therapy consisted of tisagenlecleucel in four patients and CTL119 in 10. Thirteen patients received pembrolizumab, and one received nivolumab.
Three of six patients who had early B-cell recovery re-established B-cell aplasia with the addition of a checkpoint inhibitor. In two patients, B-cell aplasia persists with ongoing pembrolizumab.
Four patients who did not respond to or relapsed after their initial CAR T-cell therapy had a partial (n=2) or complete response (n=2) with the addition of pembrolizumab.
There were additional partial responses in the remaining four patients. However, one of these patients (with CD19-dim/negative disease) progressed.
“The idea was if you can give pembrolizumab, you can take the brakes off, and maybe you can reinitiate the immune attack,” Dr. Brodsky said.
“[This is a] very small [study with] preliminary data but very exciting that it is safe to give checkpoint inhibitors with CAR T cells, and it may be efficacious at getting the immune response back.”
Tisagenlecleucel follow-up
One of the two tisagenlecleucel updates (abstract 895) consists of data from the ELIANA trial, which includes pediatric and young adult patients with relapsed/refractory ALL.
The overall response rate was 82% (65/79). Of the 65 responders, 29 were still in response at follow-up.
The probability of relapse-free survival was 66% at 12 months and 18 months.
“These are some very fast-growing tumors, and these are refractory, resistant patients, so, as we get further and further out, it’s more encouraging to see that there are durable responses,” Dr. Brodsky said.
The other tisagenlecleucel update (abstract 1684) is from the JULIET trial, which includes adults with relapsed or refractory DLBCL (n=99).
The overall response rate was 54%. The probability of relapse-free survival was 66% at 6 months and 64% at both 12 months and 18 months.
HSCT consolidation
Dr. Brodsky also discussed long-term follow-up from a phase 1/2 trial of SCRI-CAR19v1, a CD19-specific CAR T-cell product, in patients with relapsed/refractory ALL (abstract 967).
Of the 50 evaluable patients, 17 had no history of HSCT prior to CAR T-cell therapy.
Three of the 17 patients did not proceed to HSCT after CAR T-cell therapy, and two of these patients relapsed. Of the 14 patients who did undergo HSCT after CAR T-cell therapy, two relapsed.
There were 33 patients with a prior history of HSCT, and 10 of them had another HSCT after CAR T-cell therapy. Five of them are still alive and in remission.
Of the 23 patients who did not undergo another HSCT, eight are still in remission.
“This study is very small, and it’s retrospective, but it suggests that bone marrow transplant is a good way to consolidate the remission after CAR T-cell therapy,” Dr. Brodsky said.
Several studies set to be presented at the 2018 ASH Annual Meeting provide new insights regarding chimeric antigen receptor (CAR) T-cell therapies.
One study suggests ibrutinib may enhance CAR T-cell therapy in patients with chronic lymphocytic leukemia (CLL), and another suggests checkpoint inhibitors can augment CAR T-cell therapy in certain patients with B-cell acute lymphoblastic leukemia (ALL).
Two additional studies indicate that responses to tisagenlecleucel are durable in both ALL and diffuse large B-cell lymphoma (DLBCL).
A fifth study suggests hematopoietic stem cell transplant (HSCT) may reduce the risk of relapse after CAR T-cell therapy.
ASH Secretary Robert A. Brodsky, MD, of Johns Hopkins University in Baltimore, Maryland, discussed these studies during a media briefing ahead of the ASH Annual Meeting.
Ibrutinib
In the ibrutinib study (abstract 299), patients received the BTK inhibitor starting 2 weeks prior to leukapheresis and continued until 3 months after treatment with JCAR014.
Data suggest this strategy may improve responses and decrease the incidence of severe cytokine release syndrome in patients with relapsed or refractory CLL.
Responses occurred in 88% of patients who received ibrutinib and 56% of those who did not.
Grade 3-5 cytokine release syndrome occurred in 5 of 19 patients (26%) in the no-ibrutinib cohort and 0 of 17 patients in the ibrutinib cohort.
These findings are “early and preliminary but very exciting” Dr. Brodsky said.
Checkpoint inhibitors
Early results of the checkpoint inhibitor study (abstract 556) suggest that pembrolizumab or nivolumab may augment CD19-directed CAR T-cell therapy.
The 14 patients studied had early CAR T-cell loss, partial response, or no response to CAR T-cell therapy. Thirteen patients had B-cell ALL, and one had B lymphoblastic lymphoma.
CD19-directed CAR T-cell therapy consisted of tisagenlecleucel in four patients and CTL119 in 10. Thirteen patients received pembrolizumab, and one received nivolumab.
Three of six patients who had early B-cell recovery re-established B-cell aplasia with the addition of a checkpoint inhibitor. In two patients, B-cell aplasia persists with ongoing pembrolizumab.
Four patients who did not respond to or relapsed after their initial CAR T-cell therapy had a partial (n=2) or complete response (n=2) with the addition of pembrolizumab.
There were additional partial responses in the remaining four patients. However, one of these patients (with CD19-dim/negative disease) progressed.
“The idea was if you can give pembrolizumab, you can take the brakes off, and maybe you can reinitiate the immune attack,” Dr. Brodsky said.
“[This is a] very small [study with] preliminary data but very exciting that it is safe to give checkpoint inhibitors with CAR T cells, and it may be efficacious at getting the immune response back.”
Tisagenlecleucel follow-up
One of the two tisagenlecleucel updates (abstract 895) consists of data from the ELIANA trial, which includes pediatric and young adult patients with relapsed/refractory ALL.
The overall response rate was 82% (65/79). Of the 65 responders, 29 were still in response at follow-up.
The probability of relapse-free survival was 66% at 12 months and 18 months.
“These are some very fast-growing tumors, and these are refractory, resistant patients, so, as we get further and further out, it’s more encouraging to see that there are durable responses,” Dr. Brodsky said.
The other tisagenlecleucel update (abstract 1684) is from the JULIET trial, which includes adults with relapsed or refractory DLBCL (n=99).
The overall response rate was 54%. The probability of relapse-free survival was 66% at 6 months and 64% at both 12 months and 18 months.
HSCT consolidation
Dr. Brodsky also discussed long-term follow-up from a phase 1/2 trial of SCRI-CAR19v1, a CD19-specific CAR T-cell product, in patients with relapsed/refractory ALL (abstract 967).
Of the 50 evaluable patients, 17 had no history of HSCT prior to CAR T-cell therapy.
Three of the 17 patients did not proceed to HSCT after CAR T-cell therapy, and two of these patients relapsed. Of the 14 patients who did undergo HSCT after CAR T-cell therapy, two relapsed.
There were 33 patients with a prior history of HSCT, and 10 of them had another HSCT after CAR T-cell therapy. Five of them are still alive and in remission.
Of the 23 patients who did not undergo another HSCT, eight are still in remission.
“This study is very small, and it’s retrospective, but it suggests that bone marrow transplant is a good way to consolidate the remission after CAR T-cell therapy,” Dr. Brodsky said.
Several studies set to be presented at the 2018 ASH Annual Meeting provide new insights regarding chimeric antigen receptor (CAR) T-cell therapies.
One study suggests ibrutinib may enhance CAR T-cell therapy in patients with chronic lymphocytic leukemia (CLL), and another suggests checkpoint inhibitors can augment CAR T-cell therapy in certain patients with B-cell acute lymphoblastic leukemia (ALL).
Two additional studies indicate that responses to tisagenlecleucel are durable in both ALL and diffuse large B-cell lymphoma (DLBCL).
A fifth study suggests hematopoietic stem cell transplant (HSCT) may reduce the risk of relapse after CAR T-cell therapy.
ASH Secretary Robert A. Brodsky, MD, of Johns Hopkins University in Baltimore, Maryland, discussed these studies during a media briefing ahead of the ASH Annual Meeting.
Ibrutinib
In the ibrutinib study (abstract 299), patients received the BTK inhibitor starting 2 weeks prior to leukapheresis and continued until 3 months after treatment with JCAR014.
Data suggest this strategy may improve responses and decrease the incidence of severe cytokine release syndrome in patients with relapsed or refractory CLL.
Responses occurred in 88% of patients who received ibrutinib and 56% of those who did not.
Grade 3-5 cytokine release syndrome occurred in 5 of 19 patients (26%) in the no-ibrutinib cohort and 0 of 17 patients in the ibrutinib cohort.
These findings are “early and preliminary but very exciting” Dr. Brodsky said.
Checkpoint inhibitors
Early results of the checkpoint inhibitor study (abstract 556) suggest that pembrolizumab or nivolumab may augment CD19-directed CAR T-cell therapy.
The 14 patients studied had early CAR T-cell loss, partial response, or no response to CAR T-cell therapy. Thirteen patients had B-cell ALL, and one had B lymphoblastic lymphoma.
CD19-directed CAR T-cell therapy consisted of tisagenlecleucel in four patients and CTL119 in 10. Thirteen patients received pembrolizumab, and one received nivolumab.
Three of six patients who had early B-cell recovery re-established B-cell aplasia with the addition of a checkpoint inhibitor. In two patients, B-cell aplasia persists with ongoing pembrolizumab.
Four patients who did not respond to or relapsed after their initial CAR T-cell therapy had a partial (n=2) or complete response (n=2) with the addition of pembrolizumab.
There were additional partial responses in the remaining four patients. However, one of these patients (with CD19-dim/negative disease) progressed.
“The idea was if you can give pembrolizumab, you can take the brakes off, and maybe you can reinitiate the immune attack,” Dr. Brodsky said.
“[This is a] very small [study with] preliminary data but very exciting that it is safe to give checkpoint inhibitors with CAR T cells, and it may be efficacious at getting the immune response back.”
Tisagenlecleucel follow-up
One of the two tisagenlecleucel updates (abstract 895) consists of data from the ELIANA trial, which includes pediatric and young adult patients with relapsed/refractory ALL.
The overall response rate was 82% (65/79). Of the 65 responders, 29 were still in response at follow-up.
The probability of relapse-free survival was 66% at 12 months and 18 months.
“These are some very fast-growing tumors, and these are refractory, resistant patients, so, as we get further and further out, it’s more encouraging to see that there are durable responses,” Dr. Brodsky said.
The other tisagenlecleucel update (abstract 1684) is from the JULIET trial, which includes adults with relapsed or refractory DLBCL (n=99).
The overall response rate was 54%. The probability of relapse-free survival was 66% at 6 months and 64% at both 12 months and 18 months.
HSCT consolidation
Dr. Brodsky also discussed long-term follow-up from a phase 1/2 trial of SCRI-CAR19v1, a CD19-specific CAR T-cell product, in patients with relapsed/refractory ALL (abstract 967).
Of the 50 evaluable patients, 17 had no history of HSCT prior to CAR T-cell therapy.
Three of the 17 patients did not proceed to HSCT after CAR T-cell therapy, and two of these patients relapsed. Of the 14 patients who did undergo HSCT after CAR T-cell therapy, two relapsed.
There were 33 patients with a prior history of HSCT, and 10 of them had another HSCT after CAR T-cell therapy. Five of them are still alive and in remission.
Of the 23 patients who did not undergo another HSCT, eight are still in remission.
“This study is very small, and it’s retrospective, but it suggests that bone marrow transplant is a good way to consolidate the remission after CAR T-cell therapy,” Dr. Brodsky said.
Biosimilar deemed equivalent to rituximab in FL
Phase 3 results suggest the biosimilar product CT-P10 is equivalent to rituximab in patients with low-tumor-burden follicular lymphoma (FL).
Overall response rates were similar—both exceeding 80%—in patients who received CT-P10 and those who received rituximab.
In addition, adverse event (AE) profiles were comparable between the treatment arms.
Larry W. Kwak, MD, PhD, of City of Hope in Duarte, California, and his colleagues reported these results in The Lancet Haematology.
CT-P10 was approved by the European Commission in 2017 and was recommended for approval by the U.S. Food and Drug Administration’s Oncologic Drugs Advisory Committee last month.
The phase 3 trial of CT-P10 included 258 patients with stage II-IV low-tumor-burden FL. They were randomized to receive CT-P10 (n=130) or rituximab (n=128).
Patients received intravenous CT-P10 or rituximab weekly for 4 weeks as induction therapy. Patients experiencing disease control went on to a maintenance phase with their assigned treatment, given every 8 weeks for six cycles, followed by another year of maintenance therapy with CT-P10 for those still on study.
Efficacy
The overall response rate at 7 months was 83% in patients randomized to CT-P10 and 81% in those randomized to rituximab.
The complete response rates were 28% and 34%, respectively. The unconfirmed complete response rates were 5% and 2%, respectively. And the partial response rates were 51% and 46%, respectively.
The two treatments were deemed therapeutically equivalent, as the two-sided 90% confidence intervals for the difference in proportion of responders between CT-P10 and rituximab were within the prespecified equivalence margin of 17%.
Safety
Treatment-emergent AEs occurred in 71% of patients in the CT-P10 arm and 67% of those in the rituximab arm.
The most common treatment-emergent AEs (in the CT-P10 and rituximab arms, respectively) were:
- Infusion-related reactions (31% and 29%)
- Infections (27% and 21%)
- Worsening neutropenia (22% for both)
- Upper respiratory tract infection (12% and 11%)
- Worsening anemia (10% and 14%)
- Worsening thrombocytopenia (8% and 7%)
- Fatigue (7% and 9%)
- Diarrhea (5% for both)
- Nausea (5% for both)
- Urinary tract infection (4% and 5%)
- Headache (3% and 5%).
Serious AEs were reported in six patients in the CT-P10 arm and three patients in the rituximab arm.
Two serious AEs—myocardial infarction and constipation—in the CT-P10 arm were considered related to treatment. None of the serious AEs in the rituximab arm were considered treatment-related.
Two patients in the CT-P10 arm discontinued treatment due to AEs—one due to myocardial infarction and one due to dermatitis. There were no AE-related discontinuations in the rituximab arm.
There were two deaths in the CT-P10 arm as of the cutoff date (January 4, 2018). One was due to myocardial infarction, and one was due to respiratory failure. The myocardial infarction was considered possibly related to treatment.
This trial was sponsored by Celltrion, the company developing CT-P10. Three study authors are employees of the company.
Dr. Kwak and several other authors not employed by Celltrion reported disclosures related to the company. Authors also reported relationships with Novartis, Roche, AbbVie, Celgene, and Takeda, among other entities.
Phase 3 results suggest the biosimilar product CT-P10 is equivalent to rituximab in patients with low-tumor-burden follicular lymphoma (FL).
Overall response rates were similar—both exceeding 80%—in patients who received CT-P10 and those who received rituximab.
In addition, adverse event (AE) profiles were comparable between the treatment arms.
Larry W. Kwak, MD, PhD, of City of Hope in Duarte, California, and his colleagues reported these results in The Lancet Haematology.
CT-P10 was approved by the European Commission in 2017 and was recommended for approval by the U.S. Food and Drug Administration’s Oncologic Drugs Advisory Committee last month.
The phase 3 trial of CT-P10 included 258 patients with stage II-IV low-tumor-burden FL. They were randomized to receive CT-P10 (n=130) or rituximab (n=128).
Patients received intravenous CT-P10 or rituximab weekly for 4 weeks as induction therapy. Patients experiencing disease control went on to a maintenance phase with their assigned treatment, given every 8 weeks for six cycles, followed by another year of maintenance therapy with CT-P10 for those still on study.
Efficacy
The overall response rate at 7 months was 83% in patients randomized to CT-P10 and 81% in those randomized to rituximab.
The complete response rates were 28% and 34%, respectively. The unconfirmed complete response rates were 5% and 2%, respectively. And the partial response rates were 51% and 46%, respectively.
The two treatments were deemed therapeutically equivalent, as the two-sided 90% confidence intervals for the difference in proportion of responders between CT-P10 and rituximab were within the prespecified equivalence margin of 17%.
Safety
Treatment-emergent AEs occurred in 71% of patients in the CT-P10 arm and 67% of those in the rituximab arm.
The most common treatment-emergent AEs (in the CT-P10 and rituximab arms, respectively) were:
- Infusion-related reactions (31% and 29%)
- Infections (27% and 21%)
- Worsening neutropenia (22% for both)
- Upper respiratory tract infection (12% and 11%)
- Worsening anemia (10% and 14%)
- Worsening thrombocytopenia (8% and 7%)
- Fatigue (7% and 9%)
- Diarrhea (5% for both)
- Nausea (5% for both)
- Urinary tract infection (4% and 5%)
- Headache (3% and 5%).
Serious AEs were reported in six patients in the CT-P10 arm and three patients in the rituximab arm.
Two serious AEs—myocardial infarction and constipation—in the CT-P10 arm were considered related to treatment. None of the serious AEs in the rituximab arm were considered treatment-related.
Two patients in the CT-P10 arm discontinued treatment due to AEs—one due to myocardial infarction and one due to dermatitis. There were no AE-related discontinuations in the rituximab arm.
There were two deaths in the CT-P10 arm as of the cutoff date (January 4, 2018). One was due to myocardial infarction, and one was due to respiratory failure. The myocardial infarction was considered possibly related to treatment.
This trial was sponsored by Celltrion, the company developing CT-P10. Three study authors are employees of the company.
Dr. Kwak and several other authors not employed by Celltrion reported disclosures related to the company. Authors also reported relationships with Novartis, Roche, AbbVie, Celgene, and Takeda, among other entities.
Phase 3 results suggest the biosimilar product CT-P10 is equivalent to rituximab in patients with low-tumor-burden follicular lymphoma (FL).
Overall response rates were similar—both exceeding 80%—in patients who received CT-P10 and those who received rituximab.
In addition, adverse event (AE) profiles were comparable between the treatment arms.
Larry W. Kwak, MD, PhD, of City of Hope in Duarte, California, and his colleagues reported these results in The Lancet Haematology.
CT-P10 was approved by the European Commission in 2017 and was recommended for approval by the U.S. Food and Drug Administration’s Oncologic Drugs Advisory Committee last month.
The phase 3 trial of CT-P10 included 258 patients with stage II-IV low-tumor-burden FL. They were randomized to receive CT-P10 (n=130) or rituximab (n=128).
Patients received intravenous CT-P10 or rituximab weekly for 4 weeks as induction therapy. Patients experiencing disease control went on to a maintenance phase with their assigned treatment, given every 8 weeks for six cycles, followed by another year of maintenance therapy with CT-P10 for those still on study.
Efficacy
The overall response rate at 7 months was 83% in patients randomized to CT-P10 and 81% in those randomized to rituximab.
The complete response rates were 28% and 34%, respectively. The unconfirmed complete response rates were 5% and 2%, respectively. And the partial response rates were 51% and 46%, respectively.
The two treatments were deemed therapeutically equivalent, as the two-sided 90% confidence intervals for the difference in proportion of responders between CT-P10 and rituximab were within the prespecified equivalence margin of 17%.
Safety
Treatment-emergent AEs occurred in 71% of patients in the CT-P10 arm and 67% of those in the rituximab arm.
The most common treatment-emergent AEs (in the CT-P10 and rituximab arms, respectively) were:
- Infusion-related reactions (31% and 29%)
- Infections (27% and 21%)
- Worsening neutropenia (22% for both)
- Upper respiratory tract infection (12% and 11%)
- Worsening anemia (10% and 14%)
- Worsening thrombocytopenia (8% and 7%)
- Fatigue (7% and 9%)
- Diarrhea (5% for both)
- Nausea (5% for both)
- Urinary tract infection (4% and 5%)
- Headache (3% and 5%).
Serious AEs were reported in six patients in the CT-P10 arm and three patients in the rituximab arm.
Two serious AEs—myocardial infarction and constipation—in the CT-P10 arm were considered related to treatment. None of the serious AEs in the rituximab arm were considered treatment-related.
Two patients in the CT-P10 arm discontinued treatment due to AEs—one due to myocardial infarction and one due to dermatitis. There were no AE-related discontinuations in the rituximab arm.
There were two deaths in the CT-P10 arm as of the cutoff date (January 4, 2018). One was due to myocardial infarction, and one was due to respiratory failure. The myocardial infarction was considered possibly related to treatment.
This trial was sponsored by Celltrion, the company developing CT-P10. Three study authors are employees of the company.
Dr. Kwak and several other authors not employed by Celltrion reported disclosures related to the company. Authors also reported relationships with Novartis, Roche, AbbVie, Celgene, and Takeda, among other entities.
Elderly NHL patients have higher NRM after HSCT
A retrospective study suggests elderly patients with non-Hodgkin lymphoma (NHL) are more likely to die, but not relapse, within a year of allogeneic hematopoietic stem cell transplant (allo-HSCT).
The rate of non-relapse mortality (NRM) at 1 year was significantly higher for elderly patients than for middle-aged or young patients.
However, the 3-year rate of relapse was similar across the age groups.
Charalampia Kyriakou, MD, PhD, of University College London in the U.K., and her colleagues reported these findings in Biology of Blood and Marrow Transplantation.
The investigators analyzed 3,919 patients with NHL who underwent allo-HSCT between 2003 and 2013.
The patients had follicular lymphoma (n=1,461), diffuse large B-cell lymphoma (n=1,192), mantle cell lymphoma (n=823), and peripheral T-cell lymphoma (n=443).
At the time of transplant, about 85% of patients were chemo-sensitive, with the remainder being chemo-refractory.
Results
The investigators compared outcomes in patients assigned to three age groups—young (18-50), middle-aged (51-65), and elderly (66-77).
NRM at 1 year was 13% for young patients, 20% for middle-aged patients, and 33% for elderly patients (P<0.001).
Overall survival at 3 years was 60% in young patients, 54% in middle-aged patients, and 38% in the elderly (P<0.001).
In contrast to these significant associations between age and survival, the rate of relapse at 3 years remained relatively consistent—30% in young patients, 31% in middle-aged patients, and 28% in elderly patients (P=0.355).
The increased risk of NRM in elderly patients could not be fully explained by comorbidities, although these were more common in the elderly.
After analyzing information from a subset of patients, the investigators concluded that “the presence of comorbidities is a significant risk factor for NRM and survival, but this does not fully explain the outcome disadvantages in our [elderly] group.”
Therefore, age remains an independent risk factor.
The investigators did not report conflicts of interest.
A retrospective study suggests elderly patients with non-Hodgkin lymphoma (NHL) are more likely to die, but not relapse, within a year of allogeneic hematopoietic stem cell transplant (allo-HSCT).
The rate of non-relapse mortality (NRM) at 1 year was significantly higher for elderly patients than for middle-aged or young patients.
However, the 3-year rate of relapse was similar across the age groups.
Charalampia Kyriakou, MD, PhD, of University College London in the U.K., and her colleagues reported these findings in Biology of Blood and Marrow Transplantation.
The investigators analyzed 3,919 patients with NHL who underwent allo-HSCT between 2003 and 2013.
The patients had follicular lymphoma (n=1,461), diffuse large B-cell lymphoma (n=1,192), mantle cell lymphoma (n=823), and peripheral T-cell lymphoma (n=443).
At the time of transplant, about 85% of patients were chemo-sensitive, with the remainder being chemo-refractory.
Results
The investigators compared outcomes in patients assigned to three age groups—young (18-50), middle-aged (51-65), and elderly (66-77).
NRM at 1 year was 13% for young patients, 20% for middle-aged patients, and 33% for elderly patients (P<0.001).
Overall survival at 3 years was 60% in young patients, 54% in middle-aged patients, and 38% in the elderly (P<0.001).
In contrast to these significant associations between age and survival, the rate of relapse at 3 years remained relatively consistent—30% in young patients, 31% in middle-aged patients, and 28% in elderly patients (P=0.355).
The increased risk of NRM in elderly patients could not be fully explained by comorbidities, although these were more common in the elderly.
After analyzing information from a subset of patients, the investigators concluded that “the presence of comorbidities is a significant risk factor for NRM and survival, but this does not fully explain the outcome disadvantages in our [elderly] group.”
Therefore, age remains an independent risk factor.
The investigators did not report conflicts of interest.
A retrospective study suggests elderly patients with non-Hodgkin lymphoma (NHL) are more likely to die, but not relapse, within a year of allogeneic hematopoietic stem cell transplant (allo-HSCT).
The rate of non-relapse mortality (NRM) at 1 year was significantly higher for elderly patients than for middle-aged or young patients.
However, the 3-year rate of relapse was similar across the age groups.
Charalampia Kyriakou, MD, PhD, of University College London in the U.K., and her colleagues reported these findings in Biology of Blood and Marrow Transplantation.
The investigators analyzed 3,919 patients with NHL who underwent allo-HSCT between 2003 and 2013.
The patients had follicular lymphoma (n=1,461), diffuse large B-cell lymphoma (n=1,192), mantle cell lymphoma (n=823), and peripheral T-cell lymphoma (n=443).
At the time of transplant, about 85% of patients were chemo-sensitive, with the remainder being chemo-refractory.
Results
The investigators compared outcomes in patients assigned to three age groups—young (18-50), middle-aged (51-65), and elderly (66-77).
NRM at 1 year was 13% for young patients, 20% for middle-aged patients, and 33% for elderly patients (P<0.001).
Overall survival at 3 years was 60% in young patients, 54% in middle-aged patients, and 38% in the elderly (P<0.001).
In contrast to these significant associations between age and survival, the rate of relapse at 3 years remained relatively consistent—30% in young patients, 31% in middle-aged patients, and 28% in elderly patients (P=0.355).
The increased risk of NRM in elderly patients could not be fully explained by comorbidities, although these were more common in the elderly.
After analyzing information from a subset of patients, the investigators concluded that “the presence of comorbidities is a significant risk factor for NRM and survival, but this does not fully explain the outcome disadvantages in our [elderly] group.”
Therefore, age remains an independent risk factor.
The investigators did not report conflicts of interest.
Americans concerned about cost of cancer care
A recent survey suggests Americans are nearly as worried about the cost of a cancer diagnosis as they are about dying from cancer.
The cost of cancer care was a top concern even among people who had no prior experience with cancer.
At the same time, cancer patients/survivors admitted to delaying or forgoing care due to costs, and caregivers reported taking “dramatic” actions to pay for their loved one’s care.
These are findings from the American Society of Clinical Oncology (ASCO)’s second annual National Cancer Opinion Survey.
The survey was conducted online by The Harris Poll from July 10, 2018, to August 10, 2018. It included 4,887 U.S. adults age 18 and older—1,001 of whom have or had cancer.
Cost among top concerns
Death and pain/suffering were the top concerns related to a cancer diagnosis. Fifty-four percent of respondents said death would be one of their greatest concerns if they were diagnosed with cancer, and the same percentage rated pain/suffering a top concern.
Forty-four percent of respondents said paying for cancer treatment would be a top concern, and 45% said the same about the financial impact of a cancer diagnosis on their family. When combined, financial issues were a top concern for 57% of respondents.
Paying for treatment was a top concern for:
- 36% of respondents who had/have cancer
- 51% of caregivers
- 43% of people with no prior cancer experience.
The financial impact on family was a top concern for:
- 39% of respondents who had/have cancer
- 55% of caregivers
- 42% of people with no prior cancer experience.
Cutting costs
Sixty-one percent of caregivers surveyed said they or another relative have taken a “dramatic” step to help pay for their loved one’s care, including:
- Dipping into savings accounts (35%)
- Working extra hours (23%)
- Taking an early withdrawal from a retirement account or college fund (14%)
- Postponing retirement (14%)
- Taking out a second mortgage or other type of loan (13%)
- Taking an additional job (13%)
- Selling family heirlooms (9%).
Twenty percent of cancer patients/survivors said they have taken actions to reduce treatment costs, including:
- Delaying scans (7%)
- Skipping or delaying appointments (7%)
- Skipping doses of prescribed treatment (6%)
- Postponing or not filling prescriptions (5%)
- Refusing treatment (3%).
“Patients are right to be concerned about the financial impact of a cancer diagnosis on their families,” said Richard L. Schilsky, MD, ASCO’s chief medical officer.
“It’s clear that high treatment costs are taking a serious toll not only on patients, but also on the people who care for them. If a family member has been diagnosed with cancer, the sole focus should be helping them get well. Instead, Americans are worrying about affording treatment, and, in many cases, they’re making serious personal sacrifices to help pay for their loved ones’ care.”
A recent survey suggests Americans are nearly as worried about the cost of a cancer diagnosis as they are about dying from cancer.
The cost of cancer care was a top concern even among people who had no prior experience with cancer.
At the same time, cancer patients/survivors admitted to delaying or forgoing care due to costs, and caregivers reported taking “dramatic” actions to pay for their loved one’s care.
These are findings from the American Society of Clinical Oncology (ASCO)’s second annual National Cancer Opinion Survey.
The survey was conducted online by The Harris Poll from July 10, 2018, to August 10, 2018. It included 4,887 U.S. adults age 18 and older—1,001 of whom have or had cancer.
Cost among top concerns
Death and pain/suffering were the top concerns related to a cancer diagnosis. Fifty-four percent of respondents said death would be one of their greatest concerns if they were diagnosed with cancer, and the same percentage rated pain/suffering a top concern.
Forty-four percent of respondents said paying for cancer treatment would be a top concern, and 45% said the same about the financial impact of a cancer diagnosis on their family. When combined, financial issues were a top concern for 57% of respondents.
Paying for treatment was a top concern for:
- 36% of respondents who had/have cancer
- 51% of caregivers
- 43% of people with no prior cancer experience.
The financial impact on family was a top concern for:
- 39% of respondents who had/have cancer
- 55% of caregivers
- 42% of people with no prior cancer experience.
Cutting costs
Sixty-one percent of caregivers surveyed said they or another relative have taken a “dramatic” step to help pay for their loved one’s care, including:
- Dipping into savings accounts (35%)
- Working extra hours (23%)
- Taking an early withdrawal from a retirement account or college fund (14%)
- Postponing retirement (14%)
- Taking out a second mortgage or other type of loan (13%)
- Taking an additional job (13%)
- Selling family heirlooms (9%).
Twenty percent of cancer patients/survivors said they have taken actions to reduce treatment costs, including:
- Delaying scans (7%)
- Skipping or delaying appointments (7%)
- Skipping doses of prescribed treatment (6%)
- Postponing or not filling prescriptions (5%)
- Refusing treatment (3%).
“Patients are right to be concerned about the financial impact of a cancer diagnosis on their families,” said Richard L. Schilsky, MD, ASCO’s chief medical officer.
“It’s clear that high treatment costs are taking a serious toll not only on patients, but also on the people who care for them. If a family member has been diagnosed with cancer, the sole focus should be helping them get well. Instead, Americans are worrying about affording treatment, and, in many cases, they’re making serious personal sacrifices to help pay for their loved ones’ care.”
A recent survey suggests Americans are nearly as worried about the cost of a cancer diagnosis as they are about dying from cancer.
The cost of cancer care was a top concern even among people who had no prior experience with cancer.
At the same time, cancer patients/survivors admitted to delaying or forgoing care due to costs, and caregivers reported taking “dramatic” actions to pay for their loved one’s care.
These are findings from the American Society of Clinical Oncology (ASCO)’s second annual National Cancer Opinion Survey.
The survey was conducted online by The Harris Poll from July 10, 2018, to August 10, 2018. It included 4,887 U.S. adults age 18 and older—1,001 of whom have or had cancer.
Cost among top concerns
Death and pain/suffering were the top concerns related to a cancer diagnosis. Fifty-four percent of respondents said death would be one of their greatest concerns if they were diagnosed with cancer, and the same percentage rated pain/suffering a top concern.
Forty-four percent of respondents said paying for cancer treatment would be a top concern, and 45% said the same about the financial impact of a cancer diagnosis on their family. When combined, financial issues were a top concern for 57% of respondents.
Paying for treatment was a top concern for:
- 36% of respondents who had/have cancer
- 51% of caregivers
- 43% of people with no prior cancer experience.
The financial impact on family was a top concern for:
- 39% of respondents who had/have cancer
- 55% of caregivers
- 42% of people with no prior cancer experience.
Cutting costs
Sixty-one percent of caregivers surveyed said they or another relative have taken a “dramatic” step to help pay for their loved one’s care, including:
- Dipping into savings accounts (35%)
- Working extra hours (23%)
- Taking an early withdrawal from a retirement account or college fund (14%)
- Postponing retirement (14%)
- Taking out a second mortgage or other type of loan (13%)
- Taking an additional job (13%)
- Selling family heirlooms (9%).
Twenty percent of cancer patients/survivors said they have taken actions to reduce treatment costs, including:
- Delaying scans (7%)
- Skipping or delaying appointments (7%)
- Skipping doses of prescribed treatment (6%)
- Postponing or not filling prescriptions (5%)
- Refusing treatment (3%).
“Patients are right to be concerned about the financial impact of a cancer diagnosis on their families,” said Richard L. Schilsky, MD, ASCO’s chief medical officer.
“It’s clear that high treatment costs are taking a serious toll not only on patients, but also on the people who care for them. If a family member has been diagnosed with cancer, the sole focus should be helping them get well. Instead, Americans are worrying about affording treatment, and, in many cases, they’re making serious personal sacrifices to help pay for their loved ones’ care.”
Rituximab biosimilar looks equivalent in follicular lymphoma
The rituximab biosimilar CT-P10 has equivalent efficacy, compared with rituximab, and is well tolerated in the treatment of low–tumor-burden follicular lymphoma, according to results from a multinational, randomized, phase 3 study.
Overall response after 7 months of treatment exceeded 80% for patients assigned to CT-P10 and for those assigned to rituximab, investigators reported in the Lancet Haematology.
Adverse event profiles were comparable for rituximab and the biosimilar over that time period, while pharmacokinetics, pharmacodynamics, and immunogenicity were likewise comparable between arms, according to investigators.
“Thus, CT-P10 monotherapy is suggested as a new therapeutic option for patients with low–tumor-burden follicular lymphoma,” wrote senior author Larry W Kwak, MD, PhD, of the Comprehensive Cancer Center, City of Hope, Duarte, Calif., and his colleagues.
CT-P10, the first rituximab biosimilar to be authorized by the European Medicines Agency, has been recommended for approval in the United States by the Food and Drug Administration’s Oncologic Drugs Advisory Committee.
If approved by the FDA, CT-P10 would be the first rituximab biosimilar available in the United States, according to the company, which noted three proposed indications in non-Hodgkin lymphoma.
In the current randomized, double-blind, parallel-group, phase 3 trial, 258 patients with stage II-IV low–tumor-burden follicular lymphoma were randomly assigned to CT-P10 (130 patients) or rituximab sourced in the United States (128 patients).
Treatment consisted of an induction period of intravenous CT-P10 or rituximab weekly for 4 weeks, while patients experiencing disease control went on to a maintenance phase with their assigned treatment given every 8 weeks for six cycles, followed by another year of maintenance therapy with CT-P10 for those still on study.
The primary endpoint of the study was overall response at 7 months, defined as a complete response, unconfirmed complete response, or partial response.
Overall response was seen in 83% of patients randomized to CT-P10 and 81% of patients randomized to rituximab at 7 months, Dr. Kwak and his colleagues reported.
The two treatments were deemed therapeutically equivalent, as illustrated by 90% confidence intervals within a prespecified equivalence margin of 17%, investigators said.
The most common treatment-emergent adverse events in either group were infusion-related reactions, which were of grade 1-2, except for one grade 3 reaction reported in the CT-P10 group, according to the report. Other common adverse events were upper respiratory tract infections and fatigue.
Serious adverse events were reported in six patients in the CT-P10 arm and three patients in the rituximab arm.
The availability of a rituximab biosimilar is anticipated to reduce the cost of treatment and improve patient access, according to investigators.
Introduction of CT-P10 in the European Union was projected to save between 90 and 150 million euros over a year, enabling more than 12,500 new patients to be treated with the biosimilar, according to results of a budget impact analysis investigators cited in their report.
“Widespread adoption of a rituximab biosimilar could have a substantial effect on health care budgets and might also have effects at a societal level,” Dr. Kwak and his coauthors said in the report.
The trial was sponsored by Celltrion and three coauthors of the study were employees of the company. Dr. Kwak and several other coinvestigators not employed by Celltrion reported disclosures related to the company. Other disclosures provided related to Novartis, Roche, AbbVie, Celgene, and Takeda, among other entities.
SOURCE: Ogura M et al. Lancet Haematol. 2018 Nov;5(11):e543-53.
The rituximab biosimilar CT-P10 has equivalent efficacy, compared with rituximab, and is well tolerated in the treatment of low–tumor-burden follicular lymphoma, according to results from a multinational, randomized, phase 3 study.
Overall response after 7 months of treatment exceeded 80% for patients assigned to CT-P10 and for those assigned to rituximab, investigators reported in the Lancet Haematology.
Adverse event profiles were comparable for rituximab and the biosimilar over that time period, while pharmacokinetics, pharmacodynamics, and immunogenicity were likewise comparable between arms, according to investigators.
“Thus, CT-P10 monotherapy is suggested as a new therapeutic option for patients with low–tumor-burden follicular lymphoma,” wrote senior author Larry W Kwak, MD, PhD, of the Comprehensive Cancer Center, City of Hope, Duarte, Calif., and his colleagues.
CT-P10, the first rituximab biosimilar to be authorized by the European Medicines Agency, has been recommended for approval in the United States by the Food and Drug Administration’s Oncologic Drugs Advisory Committee.
If approved by the FDA, CT-P10 would be the first rituximab biosimilar available in the United States, according to the company, which noted three proposed indications in non-Hodgkin lymphoma.
In the current randomized, double-blind, parallel-group, phase 3 trial, 258 patients with stage II-IV low–tumor-burden follicular lymphoma were randomly assigned to CT-P10 (130 patients) or rituximab sourced in the United States (128 patients).
Treatment consisted of an induction period of intravenous CT-P10 or rituximab weekly for 4 weeks, while patients experiencing disease control went on to a maintenance phase with their assigned treatment given every 8 weeks for six cycles, followed by another year of maintenance therapy with CT-P10 for those still on study.
The primary endpoint of the study was overall response at 7 months, defined as a complete response, unconfirmed complete response, or partial response.
Overall response was seen in 83% of patients randomized to CT-P10 and 81% of patients randomized to rituximab at 7 months, Dr. Kwak and his colleagues reported.
The two treatments were deemed therapeutically equivalent, as illustrated by 90% confidence intervals within a prespecified equivalence margin of 17%, investigators said.
The most common treatment-emergent adverse events in either group were infusion-related reactions, which were of grade 1-2, except for one grade 3 reaction reported in the CT-P10 group, according to the report. Other common adverse events were upper respiratory tract infections and fatigue.
Serious adverse events were reported in six patients in the CT-P10 arm and three patients in the rituximab arm.
The availability of a rituximab biosimilar is anticipated to reduce the cost of treatment and improve patient access, according to investigators.
Introduction of CT-P10 in the European Union was projected to save between 90 and 150 million euros over a year, enabling more than 12,500 new patients to be treated with the biosimilar, according to results of a budget impact analysis investigators cited in their report.
“Widespread adoption of a rituximab biosimilar could have a substantial effect on health care budgets and might also have effects at a societal level,” Dr. Kwak and his coauthors said in the report.
The trial was sponsored by Celltrion and three coauthors of the study were employees of the company. Dr. Kwak and several other coinvestigators not employed by Celltrion reported disclosures related to the company. Other disclosures provided related to Novartis, Roche, AbbVie, Celgene, and Takeda, among other entities.
SOURCE: Ogura M et al. Lancet Haematol. 2018 Nov;5(11):e543-53.
The rituximab biosimilar CT-P10 has equivalent efficacy, compared with rituximab, and is well tolerated in the treatment of low–tumor-burden follicular lymphoma, according to results from a multinational, randomized, phase 3 study.
Overall response after 7 months of treatment exceeded 80% for patients assigned to CT-P10 and for those assigned to rituximab, investigators reported in the Lancet Haematology.
Adverse event profiles were comparable for rituximab and the biosimilar over that time period, while pharmacokinetics, pharmacodynamics, and immunogenicity were likewise comparable between arms, according to investigators.
“Thus, CT-P10 monotherapy is suggested as a new therapeutic option for patients with low–tumor-burden follicular lymphoma,” wrote senior author Larry W Kwak, MD, PhD, of the Comprehensive Cancer Center, City of Hope, Duarte, Calif., and his colleagues.
CT-P10, the first rituximab biosimilar to be authorized by the European Medicines Agency, has been recommended for approval in the United States by the Food and Drug Administration’s Oncologic Drugs Advisory Committee.
If approved by the FDA, CT-P10 would be the first rituximab biosimilar available in the United States, according to the company, which noted three proposed indications in non-Hodgkin lymphoma.
In the current randomized, double-blind, parallel-group, phase 3 trial, 258 patients with stage II-IV low–tumor-burden follicular lymphoma were randomly assigned to CT-P10 (130 patients) or rituximab sourced in the United States (128 patients).
Treatment consisted of an induction period of intravenous CT-P10 or rituximab weekly for 4 weeks, while patients experiencing disease control went on to a maintenance phase with their assigned treatment given every 8 weeks for six cycles, followed by another year of maintenance therapy with CT-P10 for those still on study.
The primary endpoint of the study was overall response at 7 months, defined as a complete response, unconfirmed complete response, or partial response.
Overall response was seen in 83% of patients randomized to CT-P10 and 81% of patients randomized to rituximab at 7 months, Dr. Kwak and his colleagues reported.
The two treatments were deemed therapeutically equivalent, as illustrated by 90% confidence intervals within a prespecified equivalence margin of 17%, investigators said.
The most common treatment-emergent adverse events in either group were infusion-related reactions, which were of grade 1-2, except for one grade 3 reaction reported in the CT-P10 group, according to the report. Other common adverse events were upper respiratory tract infections and fatigue.
Serious adverse events were reported in six patients in the CT-P10 arm and three patients in the rituximab arm.
The availability of a rituximab biosimilar is anticipated to reduce the cost of treatment and improve patient access, according to investigators.
Introduction of CT-P10 in the European Union was projected to save between 90 and 150 million euros over a year, enabling more than 12,500 new patients to be treated with the biosimilar, according to results of a budget impact analysis investigators cited in their report.
“Widespread adoption of a rituximab biosimilar could have a substantial effect on health care budgets and might also have effects at a societal level,” Dr. Kwak and his coauthors said in the report.
The trial was sponsored by Celltrion and three coauthors of the study were employees of the company. Dr. Kwak and several other coinvestigators not employed by Celltrion reported disclosures related to the company. Other disclosures provided related to Novartis, Roche, AbbVie, Celgene, and Takeda, among other entities.
SOURCE: Ogura M et al. Lancet Haematol. 2018 Nov;5(11):e543-53.
FROM LANCET HAEMATOLOGY
Key clinical point:
Major finding: Overall response after 7 months of treatment was seen in 83% of patients randomized to CT-P10 and 81% of patients randomized to rituximab.
Study details: Analysis of 258 patients randomized to CT-P10 or rituximab in a phase 3, double-blind, parallel-group trial.
Disclosures: The trial was sponsored by Celltrion and three coauthors of the study were employees of the company. Other study coauthors reported disclosures related to Celltrion, Novartis, Roche, AbbVie, Celgene, and Takeda, among other companies.
Source: Ogura M et al. Lancet Haematol. 2018 Nov;5(11):e543-53.
Bortezomib may overcome resistance in WM
Bortezomib may help overcome treatment resistance in patients with Waldenström’s macroglobulinemia (WM) and CXCR4 mutations, according to a new study.
Researchers assessed the impact of treatment with bortezomib and rituximab in patients with WM, based on their CXCR4 mutation status.
The team found no significant difference in progression-free survival or overall survival between patients with CXCR4 mutations and those with wild-type CXCR4.
Romanos Sklavenitis-Pistofidis, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues reported this discovery in Blood.
The researchers’ main analysis included 43 patients with WM, 17 (39.5%) of whom had a CXCR4 mutation.
All patients who carried a CXCR4 mutation also had MYD88 L265P. Ten patients had frameshift mutations, one patient had a nonsense mutation, and six patients had missense mutations.
The patients were treated with bortezomib and rituximab, either upfront (n=14) or in the relapsed/refractory (n=29) setting, as part of a phase 2 trial.
Bortezomib was given at 1.6 mg/m2 on days 1, 8, and 15 every 28 days for six cycles, and rituximab was given at 375 mg/m2 on days 1, 8, 15, and 22 during cycles one and four. Patients were taken off therapy after two cycles if they had progressive disease.
The median follow-up was 90.7 months.
The researchers found no significant difference between CXCR4-mutated and wild-type patients when it came to progression-free survival (P=0.994) or overall survival (P=0.407).
The researchers repeated their analysis after excluding six patients with missense mutations and accounting for different treatment settings and found that survival remained unchanged.
“We report, for the first time, that a bortezomib-based combination is impervious to the impact of CXCR4 mutations in a cohort of patients with WM,” the researchers wrote.
“Previously, we had shown this to be true in WM cell lines, whereby genetically engineering BCWM.1 and MWCL-1 to overexpress CXCR4 had no impact on bortezomib resistance.”
The researchers noted, however, that the mechanism at work here may be different than what is seen with bortezomib in other cancers.
“Different experiments have linked CXCR4 expression and bortezomib in a variety of ways in other hematological malignancies, including multiple myeloma,” the researchers wrote.
“However, despite the complicated association in those cancer types, in WM, there seems to be a consistently neutral effect of CXCR4 mutations on bortezomib resistance in both cell line and patient data.”
The researchers recommended that this theory be tested in a prospective trial of bortezomib-based therapy in WM patients with CXCR4 mutations.
Another thing to be determined, they said, is the role of rituximab in the survival results seen in the current analysis.
This study was supported by the National Institutes of Health, the Leukemia and Lymphoma Society, and the International Waldenström Macroglobulinemia Foundation. One of the authors reported consulting and research funding from Takeda, which markets bortezomib, and other companies.
Bortezomib may help overcome treatment resistance in patients with Waldenström’s macroglobulinemia (WM) and CXCR4 mutations, according to a new study.
Researchers assessed the impact of treatment with bortezomib and rituximab in patients with WM, based on their CXCR4 mutation status.
The team found no significant difference in progression-free survival or overall survival between patients with CXCR4 mutations and those with wild-type CXCR4.
Romanos Sklavenitis-Pistofidis, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues reported this discovery in Blood.
The researchers’ main analysis included 43 patients with WM, 17 (39.5%) of whom had a CXCR4 mutation.
All patients who carried a CXCR4 mutation also had MYD88 L265P. Ten patients had frameshift mutations, one patient had a nonsense mutation, and six patients had missense mutations.
The patients were treated with bortezomib and rituximab, either upfront (n=14) or in the relapsed/refractory (n=29) setting, as part of a phase 2 trial.
Bortezomib was given at 1.6 mg/m2 on days 1, 8, and 15 every 28 days for six cycles, and rituximab was given at 375 mg/m2 on days 1, 8, 15, and 22 during cycles one and four. Patients were taken off therapy after two cycles if they had progressive disease.
The median follow-up was 90.7 months.
The researchers found no significant difference between CXCR4-mutated and wild-type patients when it came to progression-free survival (P=0.994) or overall survival (P=0.407).
The researchers repeated their analysis after excluding six patients with missense mutations and accounting for different treatment settings and found that survival remained unchanged.
“We report, for the first time, that a bortezomib-based combination is impervious to the impact of CXCR4 mutations in a cohort of patients with WM,” the researchers wrote.
“Previously, we had shown this to be true in WM cell lines, whereby genetically engineering BCWM.1 and MWCL-1 to overexpress CXCR4 had no impact on bortezomib resistance.”
The researchers noted, however, that the mechanism at work here may be different than what is seen with bortezomib in other cancers.
“Different experiments have linked CXCR4 expression and bortezomib in a variety of ways in other hematological malignancies, including multiple myeloma,” the researchers wrote.
“However, despite the complicated association in those cancer types, in WM, there seems to be a consistently neutral effect of CXCR4 mutations on bortezomib resistance in both cell line and patient data.”
The researchers recommended that this theory be tested in a prospective trial of bortezomib-based therapy in WM patients with CXCR4 mutations.
Another thing to be determined, they said, is the role of rituximab in the survival results seen in the current analysis.
This study was supported by the National Institutes of Health, the Leukemia and Lymphoma Society, and the International Waldenström Macroglobulinemia Foundation. One of the authors reported consulting and research funding from Takeda, which markets bortezomib, and other companies.
Bortezomib may help overcome treatment resistance in patients with Waldenström’s macroglobulinemia (WM) and CXCR4 mutations, according to a new study.
Researchers assessed the impact of treatment with bortezomib and rituximab in patients with WM, based on their CXCR4 mutation status.
The team found no significant difference in progression-free survival or overall survival between patients with CXCR4 mutations and those with wild-type CXCR4.
Romanos Sklavenitis-Pistofidis, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues reported this discovery in Blood.
The researchers’ main analysis included 43 patients with WM, 17 (39.5%) of whom had a CXCR4 mutation.
All patients who carried a CXCR4 mutation also had MYD88 L265P. Ten patients had frameshift mutations, one patient had a nonsense mutation, and six patients had missense mutations.
The patients were treated with bortezomib and rituximab, either upfront (n=14) or in the relapsed/refractory (n=29) setting, as part of a phase 2 trial.
Bortezomib was given at 1.6 mg/m2 on days 1, 8, and 15 every 28 days for six cycles, and rituximab was given at 375 mg/m2 on days 1, 8, 15, and 22 during cycles one and four. Patients were taken off therapy after two cycles if they had progressive disease.
The median follow-up was 90.7 months.
The researchers found no significant difference between CXCR4-mutated and wild-type patients when it came to progression-free survival (P=0.994) or overall survival (P=0.407).
The researchers repeated their analysis after excluding six patients with missense mutations and accounting for different treatment settings and found that survival remained unchanged.
“We report, for the first time, that a bortezomib-based combination is impervious to the impact of CXCR4 mutations in a cohort of patients with WM,” the researchers wrote.
“Previously, we had shown this to be true in WM cell lines, whereby genetically engineering BCWM.1 and MWCL-1 to overexpress CXCR4 had no impact on bortezomib resistance.”
The researchers noted, however, that the mechanism at work here may be different than what is seen with bortezomib in other cancers.
“Different experiments have linked CXCR4 expression and bortezomib in a variety of ways in other hematological malignancies, including multiple myeloma,” the researchers wrote.
“However, despite the complicated association in those cancer types, in WM, there seems to be a consistently neutral effect of CXCR4 mutations on bortezomib resistance in both cell line and patient data.”
The researchers recommended that this theory be tested in a prospective trial of bortezomib-based therapy in WM patients with CXCR4 mutations.
Another thing to be determined, they said, is the role of rituximab in the survival results seen in the current analysis.
This study was supported by the National Institutes of Health, the Leukemia and Lymphoma Society, and the International Waldenström Macroglobulinemia Foundation. One of the authors reported consulting and research funding from Takeda, which markets bortezomib, and other companies.
FDA expands approval of brentuximab vedotin to PTCL
The , marking the first FDA approval of a treatment for newly-diagnosed PTCL.
The drug, which is marketed by Seattle Genetics as Adcetris, is a monoclonal antibody that binds to CD30 protein found on some cancer cells.
It was previously approved for adult patients with untreated stage III or IV classical Hodgkin lymphoma (cHL), cHL after relapse, cHL after stem cell transplant in patients at high risk for relapse or progression, systemic anaplastic large cell lymphoma (ALCL) after other treatments fail, and primary cutaneous ALCL or CD30-expressing mycosis fungoides after other treatments fail.
The expanded approval, which followed the granting of Priority Review and Breakthrough Therapy designations for the supplemental Biologic License Application, was made using the FDA’s new Real-Time Oncology Review pilot program (RTOR). This program allows for data review and communication with a sponsor prior to official application submission with the goal of speeding up the review process.
The brentuximab vedotin approval now extends to previously untreated systemic ALCL and other CD30-expressing PTCLs in combination with chemotherapy.
Approval was based on the ECHELON-2 clinical trial involving 452 patients, which demonstrated improved progression-free survival (PFS) in patients with certain types of PTCL who were treated first-line with either brentuximab vedotin plus chemotherapy with cyclophosphamide, doxorubicin, prednisone (CHP), or standard chemotherapy with CHP and vincristine (CHOP). Median PFS was 48 months vs. 21 months in the groups, respectively (hazard ratio, 0.71).
The FDA advises health care providers to “monitor patients for infusion reactions, life-threatening allergic reactions (anaphylaxis), neuropathy, fever, gastrointestinal complications, and infections,” according to a press release announcing the approval, which also states that patients should be monitored for tumor lysis syndrome, serious skin reactions, pulmonary toxicity, and hepatotoxicity.
The drug may cause harm to a developing fetus or newborn and should not be used in women who are pregnant or breastfeeding. A Boxed Warning regarding risk of progressive multifocal leukoencephalopathy is also included in the prescribing information.
The current standard of care for initial treatment of PTCL is multiagent chemotherapy – a treatment that “has not significantly changed in decades and is too often unsuccessful in leading to long-term remissions, underscoring the need for new treatments, ” Steven Horwitz, MD, of Memorial Sloan Kettering Cancer Center, New York, said in a statement issued by Seattle Genetics.
“With this approval, clinicians have the opportunity to transform the way newly diagnosed CD30-expressing PTCL patients are treated,” Dr. Horwitz said.
The ECHELON-2 data will be presented at the American Society of Hematology annual meeting in San Diego on Monday, Dec. 3, 2018.
The , marking the first FDA approval of a treatment for newly-diagnosed PTCL.
The drug, which is marketed by Seattle Genetics as Adcetris, is a monoclonal antibody that binds to CD30 protein found on some cancer cells.
It was previously approved for adult patients with untreated stage III or IV classical Hodgkin lymphoma (cHL), cHL after relapse, cHL after stem cell transplant in patients at high risk for relapse or progression, systemic anaplastic large cell lymphoma (ALCL) after other treatments fail, and primary cutaneous ALCL or CD30-expressing mycosis fungoides after other treatments fail.
The expanded approval, which followed the granting of Priority Review and Breakthrough Therapy designations for the supplemental Biologic License Application, was made using the FDA’s new Real-Time Oncology Review pilot program (RTOR). This program allows for data review and communication with a sponsor prior to official application submission with the goal of speeding up the review process.
The brentuximab vedotin approval now extends to previously untreated systemic ALCL and other CD30-expressing PTCLs in combination with chemotherapy.
Approval was based on the ECHELON-2 clinical trial involving 452 patients, which demonstrated improved progression-free survival (PFS) in patients with certain types of PTCL who were treated first-line with either brentuximab vedotin plus chemotherapy with cyclophosphamide, doxorubicin, prednisone (CHP), or standard chemotherapy with CHP and vincristine (CHOP). Median PFS was 48 months vs. 21 months in the groups, respectively (hazard ratio, 0.71).
The FDA advises health care providers to “monitor patients for infusion reactions, life-threatening allergic reactions (anaphylaxis), neuropathy, fever, gastrointestinal complications, and infections,” according to a press release announcing the approval, which also states that patients should be monitored for tumor lysis syndrome, serious skin reactions, pulmonary toxicity, and hepatotoxicity.
The drug may cause harm to a developing fetus or newborn and should not be used in women who are pregnant or breastfeeding. A Boxed Warning regarding risk of progressive multifocal leukoencephalopathy is also included in the prescribing information.
The current standard of care for initial treatment of PTCL is multiagent chemotherapy – a treatment that “has not significantly changed in decades and is too often unsuccessful in leading to long-term remissions, underscoring the need for new treatments, ” Steven Horwitz, MD, of Memorial Sloan Kettering Cancer Center, New York, said in a statement issued by Seattle Genetics.
“With this approval, clinicians have the opportunity to transform the way newly diagnosed CD30-expressing PTCL patients are treated,” Dr. Horwitz said.
The ECHELON-2 data will be presented at the American Society of Hematology annual meeting in San Diego on Monday, Dec. 3, 2018.
The , marking the first FDA approval of a treatment for newly-diagnosed PTCL.
The drug, which is marketed by Seattle Genetics as Adcetris, is a monoclonal antibody that binds to CD30 protein found on some cancer cells.
It was previously approved for adult patients with untreated stage III or IV classical Hodgkin lymphoma (cHL), cHL after relapse, cHL after stem cell transplant in patients at high risk for relapse or progression, systemic anaplastic large cell lymphoma (ALCL) after other treatments fail, and primary cutaneous ALCL or CD30-expressing mycosis fungoides after other treatments fail.
The expanded approval, which followed the granting of Priority Review and Breakthrough Therapy designations for the supplemental Biologic License Application, was made using the FDA’s new Real-Time Oncology Review pilot program (RTOR). This program allows for data review and communication with a sponsor prior to official application submission with the goal of speeding up the review process.
The brentuximab vedotin approval now extends to previously untreated systemic ALCL and other CD30-expressing PTCLs in combination with chemotherapy.
Approval was based on the ECHELON-2 clinical trial involving 452 patients, which demonstrated improved progression-free survival (PFS) in patients with certain types of PTCL who were treated first-line with either brentuximab vedotin plus chemotherapy with cyclophosphamide, doxorubicin, prednisone (CHP), or standard chemotherapy with CHP and vincristine (CHOP). Median PFS was 48 months vs. 21 months in the groups, respectively (hazard ratio, 0.71).
The FDA advises health care providers to “monitor patients for infusion reactions, life-threatening allergic reactions (anaphylaxis), neuropathy, fever, gastrointestinal complications, and infections,” according to a press release announcing the approval, which also states that patients should be monitored for tumor lysis syndrome, serious skin reactions, pulmonary toxicity, and hepatotoxicity.
The drug may cause harm to a developing fetus or newborn and should not be used in women who are pregnant or breastfeeding. A Boxed Warning regarding risk of progressive multifocal leukoencephalopathy is also included in the prescribing information.
The current standard of care for initial treatment of PTCL is multiagent chemotherapy – a treatment that “has not significantly changed in decades and is too often unsuccessful in leading to long-term remissions, underscoring the need for new treatments, ” Steven Horwitz, MD, of Memorial Sloan Kettering Cancer Center, New York, said in a statement issued by Seattle Genetics.
“With this approval, clinicians have the opportunity to transform the way newly diagnosed CD30-expressing PTCL patients are treated,” Dr. Horwitz said.
The ECHELON-2 data will be presented at the American Society of Hematology annual meeting in San Diego on Monday, Dec. 3, 2018.
Quick FDA approval for brentuximab vedotin in PTCL
The U.S. Food and Drug Administration (FDA) has approved a new indication for brentuximab vedotin (ADCETRIS®) less than 2 weeks after receiving the completed supplemental biologics license application (sBLA).
Brentuximab vedotin is now approved for use in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) to treat adults with previously untreated systemic anaplastic large-cell lymphoma or other CD30-expressing peripheral T-cell lymphomas (PTCLs), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.
The FDA granted priority review and breakthrough therapy designation to the sBLA for brentuximab vedotin in this indication.
The FDA reviewed the sBLA under the Real-Time Oncology Review Pilot Program, which led to approval less than 2 weeks after the application was submitted in full.
“The Real-Time Oncology Review program allows the FDA to access key data prior to the official submission of the application, allowing the review team to begin their review earlier and communicate with the sponsor prior to the application’s actual submission,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products.
“When the sponsor submits the completed application, the review team will already be familiar with the data and be able to conduct a more efficient, timely, and thorough review.”
Trial data
The FDA’s approval is based on results from the phase 3 ECHELON-2 trial (NCT01777152).
Seattle Genetics, Inc. and Takeda Pharmaceutical Company Limited announced results from this trial last month. Additional results are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 997).
The trial enrolled 452 patients with CD30-positive PTCL. The patients were randomized to receive brentuximab vedotin (BV) plus CHP or cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
The objective response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.003). The complete response rate was 68% and 56%, respectively (P=0.007).
Progression-free survival was significantly better in the BV-CHP arm than in the CHOP arm (hazard ratio=0.71; P=0.011), as was overall survival (hazard ratio=0.66; P=0.024).
The most common adverse events of any grade that occurred in at least 20% of patients in the BV-CHP arm were peripheral neuropathy, nausea, diarrhea, neutropenia, lymphopenia, fatigue, mucositis, constipation, alopecia, pyrexia, vomiting, and anemia.
Serious adverse events occurring in at least 2% of patients in the BV-CHP arm included febrile neutropenia, pneumonia, pyrexia, and sepsis.
Results of this trial suggest prophylactic growth factors should be given to previously untreated PTCL patients receiving BV-CHP (starting at cycle 1).
The U.S. Food and Drug Administration (FDA) has approved a new indication for brentuximab vedotin (ADCETRIS®) less than 2 weeks after receiving the completed supplemental biologics license application (sBLA).
Brentuximab vedotin is now approved for use in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) to treat adults with previously untreated systemic anaplastic large-cell lymphoma or other CD30-expressing peripheral T-cell lymphomas (PTCLs), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.
The FDA granted priority review and breakthrough therapy designation to the sBLA for brentuximab vedotin in this indication.
The FDA reviewed the sBLA under the Real-Time Oncology Review Pilot Program, which led to approval less than 2 weeks after the application was submitted in full.
“The Real-Time Oncology Review program allows the FDA to access key data prior to the official submission of the application, allowing the review team to begin their review earlier and communicate with the sponsor prior to the application’s actual submission,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products.
“When the sponsor submits the completed application, the review team will already be familiar with the data and be able to conduct a more efficient, timely, and thorough review.”
Trial data
The FDA’s approval is based on results from the phase 3 ECHELON-2 trial (NCT01777152).
Seattle Genetics, Inc. and Takeda Pharmaceutical Company Limited announced results from this trial last month. Additional results are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 997).
The trial enrolled 452 patients with CD30-positive PTCL. The patients were randomized to receive brentuximab vedotin (BV) plus CHP or cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
The objective response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.003). The complete response rate was 68% and 56%, respectively (P=0.007).
Progression-free survival was significantly better in the BV-CHP arm than in the CHOP arm (hazard ratio=0.71; P=0.011), as was overall survival (hazard ratio=0.66; P=0.024).
The most common adverse events of any grade that occurred in at least 20% of patients in the BV-CHP arm were peripheral neuropathy, nausea, diarrhea, neutropenia, lymphopenia, fatigue, mucositis, constipation, alopecia, pyrexia, vomiting, and anemia.
Serious adverse events occurring in at least 2% of patients in the BV-CHP arm included febrile neutropenia, pneumonia, pyrexia, and sepsis.
Results of this trial suggest prophylactic growth factors should be given to previously untreated PTCL patients receiving BV-CHP (starting at cycle 1).
The U.S. Food and Drug Administration (FDA) has approved a new indication for brentuximab vedotin (ADCETRIS®) less than 2 weeks after receiving the completed supplemental biologics license application (sBLA).
Brentuximab vedotin is now approved for use in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) to treat adults with previously untreated systemic anaplastic large-cell lymphoma or other CD30-expressing peripheral T-cell lymphomas (PTCLs), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.
The FDA granted priority review and breakthrough therapy designation to the sBLA for brentuximab vedotin in this indication.
The FDA reviewed the sBLA under the Real-Time Oncology Review Pilot Program, which led to approval less than 2 weeks after the application was submitted in full.
“The Real-Time Oncology Review program allows the FDA to access key data prior to the official submission of the application, allowing the review team to begin their review earlier and communicate with the sponsor prior to the application’s actual submission,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products.
“When the sponsor submits the completed application, the review team will already be familiar with the data and be able to conduct a more efficient, timely, and thorough review.”
Trial data
The FDA’s approval is based on results from the phase 3 ECHELON-2 trial (NCT01777152).
Seattle Genetics, Inc. and Takeda Pharmaceutical Company Limited announced results from this trial last month. Additional results are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 997).
The trial enrolled 452 patients with CD30-positive PTCL. The patients were randomized to receive brentuximab vedotin (BV) plus CHP or cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
The objective response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.003). The complete response rate was 68% and 56%, respectively (P=0.007).
Progression-free survival was significantly better in the BV-CHP arm than in the CHOP arm (hazard ratio=0.71; P=0.011), as was overall survival (hazard ratio=0.66; P=0.024).
The most common adverse events of any grade that occurred in at least 20% of patients in the BV-CHP arm were peripheral neuropathy, nausea, diarrhea, neutropenia, lymphopenia, fatigue, mucositis, constipation, alopecia, pyrexia, vomiting, and anemia.
Serious adverse events occurring in at least 2% of patients in the BV-CHP arm included febrile neutropenia, pneumonia, pyrexia, and sepsis.
Results of this trial suggest prophylactic growth factors should be given to previously untreated PTCL patients receiving BV-CHP (starting at cycle 1).
R-CHOP effective as first-line treatment in FL
Long-term data suggest R-CHOP can be effective as first-line treatment for patients with follicular lymphoma (FL).
In a phase 2-3 trial, investigators compared R-CHOP-21 and R-CHOP-14 in a cohort of patients with indolent lymphomas, most of whom had FL.
Ten-year survival rates were similar between the R-CHOP-21 and R-CHOP-14 groups, with progression-free survival (PFS) rates of 33% and 39%, respectively, and overall survival (OS) rates of 81% and 85%, respectively.
The investigators did note that 9% of patients in each treatment group developed secondary malignancies, and grade 3 infections were a concern as well.
Takashi Watanabe, MD, PhD, of Mie University in Japan, and his colleagues reported these results in The Lancet Haematology.
The trial (JCOG0203) included 300 patients with stage III or IV indolent B-cell lymphomas from 44 Japanese hospitals.
Most patients (n=248) had grade 1-3a FL, 17 had grade 3b FL, 6 had marginal zone lymphoma, 6 had diffuse large B-cell lymphoma, 4 had mantle cell lymphoma, 2 had small lymphocytic lymphoma, 1 had plasmacytoma, 13 had other indolent B-cell lymphomas, and 3 had other lymphomas.
The patients were randomly assigned to receive six cycles of R-CHOP 21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone every 3 weeks) or R-CHOP 14 (R-CHOP every 2 weeks with granulocyte-colony stimulating factor support). Neither group received rituximab maintenance.
Overall results
The median follow-up was 11.2 years (interquartile range, 10.1 to 12.7 years).
The 10-year PFS was 33% in the R-CHOP-21 group and 39% in the R-CHOP-14 group (hazard ratio=0.89). The 10-year OS was 81% and 85%, respectively (hazard ratio=0.87).
At 10 years, the incidence of secondary malignancies was 9% in both the R-CHOP-21 group (14/148) and the R-CHOP-14 group (14/151).
The most frequent solid tumor malignancies were stomach (n=5), lung (n=4), colon (n=3), bladder (n=2), and prostate (n=2) cancers. Hematologic malignancies included myelodysplastic syndromes (n=6), acute myeloid leukemia (n=2), acute lymphoblastic leukemia (n=1), and chronic myeloid leukemia (n=1).
There were nine deaths from secondary malignancies, four in the R-CHOP-21 group and five in the R-CHOP-14 group.
The rate of grade 3 adverse events was 18% (n=53) for the entire cohort. Grade 3 infections occurred in 23% of the R-CHOP-21 group and 12% of the R-CHOP-14 group.
Focus on grade 1-3a FL
Among the 248 patients with grade 1-3a FL, the PFS (for both treatment groups) was 45% at 5 years, 39% at 8 years, and 36% at 10 years. The OS was 94% at 5 years, 87% at 8 years, and 85% at 10 years.
Histological transformation was observed in 11% of the patients who had grade 1-3a FL at enrollment. The cumulative incidence of histological transformation was 2.4% at 3 years, 3.2% at 5 years, 8.5% at 8 years, and 9.3% at 10 years.
Secondary malignancies occurred in 10% (12/125) of the R-CHOP-21 group and 11% (13/123) of the R-CHOP-14 group.
The cumulative incidence of hematologic secondary malignancies at 10 years was 2.9%.
The investigators noted that the actual incidence of secondary solid tumors or hematologic malignancies apart from the setting of autologous stem cell transplants is not known. They emphasized that patients should be followed beyond 10 years to ensure the risk of secondary malignancies is not underestimated.
“Clinicians choosing a first-line treatment for patients with follicular lymphoma should be cautious of secondary malignancies caused by immunochemotherapy and severe complications of infectious diseases in the long-term follow-up—both of which could lead to death,” the investigators wrote.
This study was supported by the Ministry of Health, Labour and Welfare of Japan and the National Cancer Center Research and Development Fund of Japan.
Dr. Wantanabe has received honoraria from Bristol-Myers Squibb, Takeda, Taisho Toyama, Celgene, Nippon Shinyaku, and Novartis and funding resources from TakaraBio and United Immunity to support the Department of Immuno-Gene Therapy at Mie University. Multiple co-authors reported similar relationships.
Long-term data suggest R-CHOP can be effective as first-line treatment for patients with follicular lymphoma (FL).
In a phase 2-3 trial, investigators compared R-CHOP-21 and R-CHOP-14 in a cohort of patients with indolent lymphomas, most of whom had FL.
Ten-year survival rates were similar between the R-CHOP-21 and R-CHOP-14 groups, with progression-free survival (PFS) rates of 33% and 39%, respectively, and overall survival (OS) rates of 81% and 85%, respectively.
The investigators did note that 9% of patients in each treatment group developed secondary malignancies, and grade 3 infections were a concern as well.
Takashi Watanabe, MD, PhD, of Mie University in Japan, and his colleagues reported these results in The Lancet Haematology.
The trial (JCOG0203) included 300 patients with stage III or IV indolent B-cell lymphomas from 44 Japanese hospitals.
Most patients (n=248) had grade 1-3a FL, 17 had grade 3b FL, 6 had marginal zone lymphoma, 6 had diffuse large B-cell lymphoma, 4 had mantle cell lymphoma, 2 had small lymphocytic lymphoma, 1 had plasmacytoma, 13 had other indolent B-cell lymphomas, and 3 had other lymphomas.
The patients were randomly assigned to receive six cycles of R-CHOP 21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone every 3 weeks) or R-CHOP 14 (R-CHOP every 2 weeks with granulocyte-colony stimulating factor support). Neither group received rituximab maintenance.
Overall results
The median follow-up was 11.2 years (interquartile range, 10.1 to 12.7 years).
The 10-year PFS was 33% in the R-CHOP-21 group and 39% in the R-CHOP-14 group (hazard ratio=0.89). The 10-year OS was 81% and 85%, respectively (hazard ratio=0.87).
At 10 years, the incidence of secondary malignancies was 9% in both the R-CHOP-21 group (14/148) and the R-CHOP-14 group (14/151).
The most frequent solid tumor malignancies were stomach (n=5), lung (n=4), colon (n=3), bladder (n=2), and prostate (n=2) cancers. Hematologic malignancies included myelodysplastic syndromes (n=6), acute myeloid leukemia (n=2), acute lymphoblastic leukemia (n=1), and chronic myeloid leukemia (n=1).
There were nine deaths from secondary malignancies, four in the R-CHOP-21 group and five in the R-CHOP-14 group.
The rate of grade 3 adverse events was 18% (n=53) for the entire cohort. Grade 3 infections occurred in 23% of the R-CHOP-21 group and 12% of the R-CHOP-14 group.
Focus on grade 1-3a FL
Among the 248 patients with grade 1-3a FL, the PFS (for both treatment groups) was 45% at 5 years, 39% at 8 years, and 36% at 10 years. The OS was 94% at 5 years, 87% at 8 years, and 85% at 10 years.
Histological transformation was observed in 11% of the patients who had grade 1-3a FL at enrollment. The cumulative incidence of histological transformation was 2.4% at 3 years, 3.2% at 5 years, 8.5% at 8 years, and 9.3% at 10 years.
Secondary malignancies occurred in 10% (12/125) of the R-CHOP-21 group and 11% (13/123) of the R-CHOP-14 group.
The cumulative incidence of hematologic secondary malignancies at 10 years was 2.9%.
The investigators noted that the actual incidence of secondary solid tumors or hematologic malignancies apart from the setting of autologous stem cell transplants is not known. They emphasized that patients should be followed beyond 10 years to ensure the risk of secondary malignancies is not underestimated.
“Clinicians choosing a first-line treatment for patients with follicular lymphoma should be cautious of secondary malignancies caused by immunochemotherapy and severe complications of infectious diseases in the long-term follow-up—both of which could lead to death,” the investigators wrote.
This study was supported by the Ministry of Health, Labour and Welfare of Japan and the National Cancer Center Research and Development Fund of Japan.
Dr. Wantanabe has received honoraria from Bristol-Myers Squibb, Takeda, Taisho Toyama, Celgene, Nippon Shinyaku, and Novartis and funding resources from TakaraBio and United Immunity to support the Department of Immuno-Gene Therapy at Mie University. Multiple co-authors reported similar relationships.
Long-term data suggest R-CHOP can be effective as first-line treatment for patients with follicular lymphoma (FL).
In a phase 2-3 trial, investigators compared R-CHOP-21 and R-CHOP-14 in a cohort of patients with indolent lymphomas, most of whom had FL.
Ten-year survival rates were similar between the R-CHOP-21 and R-CHOP-14 groups, with progression-free survival (PFS) rates of 33% and 39%, respectively, and overall survival (OS) rates of 81% and 85%, respectively.
The investigators did note that 9% of patients in each treatment group developed secondary malignancies, and grade 3 infections were a concern as well.
Takashi Watanabe, MD, PhD, of Mie University in Japan, and his colleagues reported these results in The Lancet Haematology.
The trial (JCOG0203) included 300 patients with stage III or IV indolent B-cell lymphomas from 44 Japanese hospitals.
Most patients (n=248) had grade 1-3a FL, 17 had grade 3b FL, 6 had marginal zone lymphoma, 6 had diffuse large B-cell lymphoma, 4 had mantle cell lymphoma, 2 had small lymphocytic lymphoma, 1 had plasmacytoma, 13 had other indolent B-cell lymphomas, and 3 had other lymphomas.
The patients were randomly assigned to receive six cycles of R-CHOP 21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone every 3 weeks) or R-CHOP 14 (R-CHOP every 2 weeks with granulocyte-colony stimulating factor support). Neither group received rituximab maintenance.
Overall results
The median follow-up was 11.2 years (interquartile range, 10.1 to 12.7 years).
The 10-year PFS was 33% in the R-CHOP-21 group and 39% in the R-CHOP-14 group (hazard ratio=0.89). The 10-year OS was 81% and 85%, respectively (hazard ratio=0.87).
At 10 years, the incidence of secondary malignancies was 9% in both the R-CHOP-21 group (14/148) and the R-CHOP-14 group (14/151).
The most frequent solid tumor malignancies were stomach (n=5), lung (n=4), colon (n=3), bladder (n=2), and prostate (n=2) cancers. Hematologic malignancies included myelodysplastic syndromes (n=6), acute myeloid leukemia (n=2), acute lymphoblastic leukemia (n=1), and chronic myeloid leukemia (n=1).
There were nine deaths from secondary malignancies, four in the R-CHOP-21 group and five in the R-CHOP-14 group.
The rate of grade 3 adverse events was 18% (n=53) for the entire cohort. Grade 3 infections occurred in 23% of the R-CHOP-21 group and 12% of the R-CHOP-14 group.
Focus on grade 1-3a FL
Among the 248 patients with grade 1-3a FL, the PFS (for both treatment groups) was 45% at 5 years, 39% at 8 years, and 36% at 10 years. The OS was 94% at 5 years, 87% at 8 years, and 85% at 10 years.
Histological transformation was observed in 11% of the patients who had grade 1-3a FL at enrollment. The cumulative incidence of histological transformation was 2.4% at 3 years, 3.2% at 5 years, 8.5% at 8 years, and 9.3% at 10 years.
Secondary malignancies occurred in 10% (12/125) of the R-CHOP-21 group and 11% (13/123) of the R-CHOP-14 group.
The cumulative incidence of hematologic secondary malignancies at 10 years was 2.9%.
The investigators noted that the actual incidence of secondary solid tumors or hematologic malignancies apart from the setting of autologous stem cell transplants is not known. They emphasized that patients should be followed beyond 10 years to ensure the risk of secondary malignancies is not underestimated.
“Clinicians choosing a first-line treatment for patients with follicular lymphoma should be cautious of secondary malignancies caused by immunochemotherapy and severe complications of infectious diseases in the long-term follow-up—both of which could lead to death,” the investigators wrote.
This study was supported by the Ministry of Health, Labour and Welfare of Japan and the National Cancer Center Research and Development Fund of Japan.
Dr. Wantanabe has received honoraria from Bristol-Myers Squibb, Takeda, Taisho Toyama, Celgene, Nippon Shinyaku, and Novartis and funding resources from TakaraBio and United Immunity to support the Department of Immuno-Gene Therapy at Mie University. Multiple co-authors reported similar relationships.
R-CHOP looks viable as first line in follicular lymphoma
A decade of follow-up data suggest that patients with newly diagnosed follicular lymphoma may derive long-term benefit from first-line therapy with the R-CHOP regimen, according to investigators in Japan.
Among patients with untreated follicular and other indolent B-cell lymphomas enrolled in a randomized phase 2/3 trial, the 10-year progression-free survival (PFS) rate for patients assigned to R-CHOP-21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone every 3 weeks) was 33%, and the 10-year PFS rate for patients assigned to R-CHOP-14 (R-CHOP every 2 weeks with granulocyte colony-stimulating factor [G-CSF] support] was 39%, and these PFS rates did not differ between the treatment arms, Takashi Watanabe, MD, PhD, from Mie University in Tsu, Japan, and his colleagues reported in the Lancet Haematology.
They also found that, compared with therapeutic regimens prior to the introduction of rituximab, R-CHOP was associated with a reduced likelihood of histological transformation of follicular lymphoma into a poor-prognosis diffuse large B-cell lymphoma (DLBCL), with no apparent increase in risk of secondary malignancies.
“The gold-standard, first-line treatment in patients with advanced-stage follicular lymphoma remains undetermined. However, because of the reduction in incidence of transformation without an increase in either secondary malignancies or fatal infectious events, the R-CHOP regimen should be a candidate for standard treatment, particularly from the viewpoint of long-term follow-up,” the investigators wrote
The JCOG0203 trial, which began enrollment in September 2002, included patients with stage III or IV indolent B-cell lymphomas, including grades 1-3 follicular lymphoma, from 44 Japanese hospitals. The patients were randomly assigned to receive six cycles of either R-CHOP-14 plus G-CSF or R-CHOP-21 administered once daily for 6 days beginning on day 8 of every cycle). Patients did not receive rituximab maintenance in either group.
In the primary analysis of the trial, published in 2011, the investigators reported that in 299 patients there were no significant differences in either PFS or 6-year overall survival (OS).
In the current analysis, the investigators reported that, for 248 patients with grade 1-3a follicular lymphoma, the 8-year PFS rate was 39% and the 10-year PFS rate was 36%.
The cumulative incidence of histological transformation was 3.2% at 5 years, 8.5% at 8 years, and 9.3% 10 years after the last patient was enrolled.
“In our study, survival after histological transformation was still poor; therefore, reducing histological transformation remains a crucial issue for patients with follicular lymphoma,” the investigators wrote.
The cumulative incidence of secondary malignancies at 10 years was 8.1%, and the cumulative incidence of hematological secondary malignancies was 2.9%.
The investigators noted that the actual incidence of secondary solid tumors or hematologic malignancies apart from the setting of autologous stem cell transplants is not known and emphasized that patients should be followed beyond 10 years to ensure that the risk of secondary malignancies is not underestimated.
“Clinicians choosing a first-line treatment for patients with follicular lymphoma should be cautious of secondary malignancies caused by immunochemotherapy and severe complications of infectious diseases in the long-term follow-up – both of which could lead to death,” they advised.
The study was supported by the Ministry of Health, Labour and Welfare of Japan and by the National Cancer Center Research and Development Fund of Japan. Dr. Watanabe has received honoraria from Bristol-Myers Squibb, Takeda, Taisho Toyama, Celgene, Nippon Shinyaku, and Novartis and funding resources from TakaraBio and United Immunity to support the Department of Immuno-Gene Therapy at Mie University. Multiple coauthors reported similar relationships.
SOURCE: Watanabe T et al. Lancet Haematol. 2018 Nov;5(11):e520-31.
A decade of follow-up data suggest that patients with newly diagnosed follicular lymphoma may derive long-term benefit from first-line therapy with the R-CHOP regimen, according to investigators in Japan.
Among patients with untreated follicular and other indolent B-cell lymphomas enrolled in a randomized phase 2/3 trial, the 10-year progression-free survival (PFS) rate for patients assigned to R-CHOP-21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone every 3 weeks) was 33%, and the 10-year PFS rate for patients assigned to R-CHOP-14 (R-CHOP every 2 weeks with granulocyte colony-stimulating factor [G-CSF] support] was 39%, and these PFS rates did not differ between the treatment arms, Takashi Watanabe, MD, PhD, from Mie University in Tsu, Japan, and his colleagues reported in the Lancet Haematology.
They also found that, compared with therapeutic regimens prior to the introduction of rituximab, R-CHOP was associated with a reduced likelihood of histological transformation of follicular lymphoma into a poor-prognosis diffuse large B-cell lymphoma (DLBCL), with no apparent increase in risk of secondary malignancies.
“The gold-standard, first-line treatment in patients with advanced-stage follicular lymphoma remains undetermined. However, because of the reduction in incidence of transformation without an increase in either secondary malignancies or fatal infectious events, the R-CHOP regimen should be a candidate for standard treatment, particularly from the viewpoint of long-term follow-up,” the investigators wrote
The JCOG0203 trial, which began enrollment in September 2002, included patients with stage III or IV indolent B-cell lymphomas, including grades 1-3 follicular lymphoma, from 44 Japanese hospitals. The patients were randomly assigned to receive six cycles of either R-CHOP-14 plus G-CSF or R-CHOP-21 administered once daily for 6 days beginning on day 8 of every cycle). Patients did not receive rituximab maintenance in either group.
In the primary analysis of the trial, published in 2011, the investigators reported that in 299 patients there were no significant differences in either PFS or 6-year overall survival (OS).
In the current analysis, the investigators reported that, for 248 patients with grade 1-3a follicular lymphoma, the 8-year PFS rate was 39% and the 10-year PFS rate was 36%.
The cumulative incidence of histological transformation was 3.2% at 5 years, 8.5% at 8 years, and 9.3% 10 years after the last patient was enrolled.
“In our study, survival after histological transformation was still poor; therefore, reducing histological transformation remains a crucial issue for patients with follicular lymphoma,” the investigators wrote.
The cumulative incidence of secondary malignancies at 10 years was 8.1%, and the cumulative incidence of hematological secondary malignancies was 2.9%.
The investigators noted that the actual incidence of secondary solid tumors or hematologic malignancies apart from the setting of autologous stem cell transplants is not known and emphasized that patients should be followed beyond 10 years to ensure that the risk of secondary malignancies is not underestimated.
“Clinicians choosing a first-line treatment for patients with follicular lymphoma should be cautious of secondary malignancies caused by immunochemotherapy and severe complications of infectious diseases in the long-term follow-up – both of which could lead to death,” they advised.
The study was supported by the Ministry of Health, Labour and Welfare of Japan and by the National Cancer Center Research and Development Fund of Japan. Dr. Watanabe has received honoraria from Bristol-Myers Squibb, Takeda, Taisho Toyama, Celgene, Nippon Shinyaku, and Novartis and funding resources from TakaraBio and United Immunity to support the Department of Immuno-Gene Therapy at Mie University. Multiple coauthors reported similar relationships.
SOURCE: Watanabe T et al. Lancet Haematol. 2018 Nov;5(11):e520-31.
A decade of follow-up data suggest that patients with newly diagnosed follicular lymphoma may derive long-term benefit from first-line therapy with the R-CHOP regimen, according to investigators in Japan.
Among patients with untreated follicular and other indolent B-cell lymphomas enrolled in a randomized phase 2/3 trial, the 10-year progression-free survival (PFS) rate for patients assigned to R-CHOP-21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone every 3 weeks) was 33%, and the 10-year PFS rate for patients assigned to R-CHOP-14 (R-CHOP every 2 weeks with granulocyte colony-stimulating factor [G-CSF] support] was 39%, and these PFS rates did not differ between the treatment arms, Takashi Watanabe, MD, PhD, from Mie University in Tsu, Japan, and his colleagues reported in the Lancet Haematology.
They also found that, compared with therapeutic regimens prior to the introduction of rituximab, R-CHOP was associated with a reduced likelihood of histological transformation of follicular lymphoma into a poor-prognosis diffuse large B-cell lymphoma (DLBCL), with no apparent increase in risk of secondary malignancies.
“The gold-standard, first-line treatment in patients with advanced-stage follicular lymphoma remains undetermined. However, because of the reduction in incidence of transformation without an increase in either secondary malignancies or fatal infectious events, the R-CHOP regimen should be a candidate for standard treatment, particularly from the viewpoint of long-term follow-up,” the investigators wrote
The JCOG0203 trial, which began enrollment in September 2002, included patients with stage III or IV indolent B-cell lymphomas, including grades 1-3 follicular lymphoma, from 44 Japanese hospitals. The patients were randomly assigned to receive six cycles of either R-CHOP-14 plus G-CSF or R-CHOP-21 administered once daily for 6 days beginning on day 8 of every cycle). Patients did not receive rituximab maintenance in either group.
In the primary analysis of the trial, published in 2011, the investigators reported that in 299 patients there were no significant differences in either PFS or 6-year overall survival (OS).
In the current analysis, the investigators reported that, for 248 patients with grade 1-3a follicular lymphoma, the 8-year PFS rate was 39% and the 10-year PFS rate was 36%.
The cumulative incidence of histological transformation was 3.2% at 5 years, 8.5% at 8 years, and 9.3% 10 years after the last patient was enrolled.
“In our study, survival after histological transformation was still poor; therefore, reducing histological transformation remains a crucial issue for patients with follicular lymphoma,” the investigators wrote.
The cumulative incidence of secondary malignancies at 10 years was 8.1%, and the cumulative incidence of hematological secondary malignancies was 2.9%.
The investigators noted that the actual incidence of secondary solid tumors or hematologic malignancies apart from the setting of autologous stem cell transplants is not known and emphasized that patients should be followed beyond 10 years to ensure that the risk of secondary malignancies is not underestimated.
“Clinicians choosing a first-line treatment for patients with follicular lymphoma should be cautious of secondary malignancies caused by immunochemotherapy and severe complications of infectious diseases in the long-term follow-up – both of which could lead to death,” they advised.
The study was supported by the Ministry of Health, Labour and Welfare of Japan and by the National Cancer Center Research and Development Fund of Japan. Dr. Watanabe has received honoraria from Bristol-Myers Squibb, Takeda, Taisho Toyama, Celgene, Nippon Shinyaku, and Novartis and funding resources from TakaraBio and United Immunity to support the Department of Immuno-Gene Therapy at Mie University. Multiple coauthors reported similar relationships.
SOURCE: Watanabe T et al. Lancet Haematol. 2018 Nov;5(11):e520-31.
FROM LANCET HAEMATOLOGY
Key clinical point:
Major finding: Approximately one-third of patients treated with R-CHOP-14 plus G-CSF or R-CHOP-21 had no disease progression after 10 years of follow-up.
Study details: Long-term analysis of a randomized phase 2/3 trial in 299 patients with indolent B-cell lymphomas, including follicular lymphoma.
Disclosures: The study was supported by the Ministry of Health, Labor and Welfare of Japan and by the National Cancer Center Research and Development Fund of Japan. Dr. Wantanabe has received honoraria from Bristol-Myers Squibb, Takeda, Taisho Toyama, Celgene, Nippon Shinyaku, and Novartis and funding resources from TakaraBio and United Immunity to support the Department of Immuno-Gene Therapy in Mie University. Multiple coauthors reported similar relationships.
Source: Wantanabe T et al. Lancet Haematol. 2018 Nov;5(11):e520-31.