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VSTs can treat 5 different viral infections after HSCT
New research suggests virus-specific T cells (VSTs) can protect patients from severe viral infections that sometimes occur after hematopoietic stem cell transplant (HSCT).
The VSTs proved effective against 5 different viruses—Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6).
Ifigeneia Tzannou, MD, of Baylor College of Medicine in Houston, Texas, and her colleagues reported these findings in the Journal of Clinical Oncology.
“In this study, we continued our previous work . . . in which we showed that patients who had developed an Epstein-Barr virus infection after a transplant . . . could be helped by receiving immune cells specialized in eliminating that particular virus,” Dr Tzannou said. “Then, we and others successfully targeted other viruses—namely, adenoviruses and cytomegalovirus.”
“The novel contribution of this study is that we have targeted additional viruses, the BK virus and the HHV-6 virus, which had not been targeted this way before,” added study author Bilal Omer, MD, of Baylor College of Medicine.
“This is important because the BK virus does not have an effective treatment, and the complications are significant, including severe pain and bleeding. These patients are in the hospital for weeks, months sometimes, and, now, we have a treatment option.”
The researchers tested their VSTs in a phase 2 trial of 38 HSCT recipients with at least 1 of the aforementioned viruses.
“[To prepare the VSTs,] we take blood from healthy donors who have already been exposed to these viruses and who we have confirmed have immune cells that can fight the infections,” Dr Tzannou said.
“We isolate the cells and let them multiply in culture. The final product is a mixture of cells that, together, can target all 5 viruses. We prepared 59 sets of virus-specific cells from different donors following this procedure.”
“Our strategy is to prepare a number of sets of virus-specific cells ahead of time and store them in a freezer, ready to use when a patient needs them,” Dr Omer noted. “To match patient and donor, we use elaborate matching algorithms.”
Patients
The trial included 38 patients who had undergone HSCT to treat acute myeloid leukemia/myelodysplastic syndromes (n=20), acute lymphoblastic leukemia (n=9), lymphoma/myeloma (n=3), or nonmalignant disorders (n=6).
These 38 patients had a total of 45 infections—CMV (n=17), EBV (n=2), AdV (n=7), BKV (n=16), and HHV-6 (n=3).
Response
The researchers monitored virus levels and other clinical responses in the 37 evaluable patients.
Six weeks after the first VST infusion, the overall response rate was 91.9%.
Seventeen patients received VSTs for persistent CMV. Sixteen of these patients (94.1%) responded, 6 with complete responses (CRs) and 10 with partial responses (PRs).
Two patients received VSTs for EBV, and both achieved a virologic CR.
Seven patients received VSTs for persistent AdV. The response rate was 71.4%. Four patients achieved a CR, 1 had a PR, and 2 patients did not respond.
Three patients received VSTs to treat HHV-6 reactivations. The response rate was 67%. Two patients had a PR, and 1 was not evaluable.
Sixteen patients received VSTs for BKV-associated hemorrhagic cystitis (n= 14) or BKV-associated nephritis (n=2).
All 16 patients responded. One had a clinical and virologic CR. Six had a clinical CR but a virologic PR. Seven had a virologic and clinical PR. And 2 patients had only a virologic PR.
A total of 15 patients received a second VST infusion—1 due to lack of response, 7 who had a PR, and 7 due to recurrence. Ten of these patients responded to the second infusion—1 with a CR and 9 with a PR.
Four patients received a third infusion of VSTs. Two achieved a CR, 1 had a PR, and 1 did not respond.
Toxicity
One patient developed an isolated fever within 24 hours of VST infusion, but the researchers did not observe any other immediate toxicities.
One of the patients with BKV-associated hemorrhagic cystitis experienced transient hydronephrosis and a decrease in renal function associated with a concomitant bacterial urinary tract infection.
Nineteen patients had prior grade 2 to 4 graft-versus-host disease (GVHD)—15 with grade 2 and 4 with grade 3. All GVHD was quiescent at the time of VST infusion.
One patient developed recurrent grade 3 gastrointestinal GVHD after VST infusion and rapid corticosteroid taper. Five patients developed recurrent (n=3) or de novo (n=2) grade 1 to 2 skin GVHD, which resolved with topical treatment (n=4) and reinitiation of corticosteroid treatment (n=1).
Two patients had a flare of upper-gastrointestinal GVHD, which resolved after a brief corticosteroid course.
“We didn’t have any significant toxicities,” Dr Tzannou said. “Taken together, the results of this trial suggest that it is reasonable to consider this treatment as an early option for these patients. We hope that the results of a future multicenter, phase 3 clinical trial will help raise awareness in both physicians and patients that this treatment, which is safe and effective, is available.” 
New research suggests virus-specific T cells (VSTs) can protect patients from severe viral infections that sometimes occur after hematopoietic stem cell transplant (HSCT).
The VSTs proved effective against 5 different viruses—Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6).
Ifigeneia Tzannou, MD, of Baylor College of Medicine in Houston, Texas, and her colleagues reported these findings in the Journal of Clinical Oncology.
“In this study, we continued our previous work . . . in which we showed that patients who had developed an Epstein-Barr virus infection after a transplant . . . could be helped by receiving immune cells specialized in eliminating that particular virus,” Dr Tzannou said. “Then, we and others successfully targeted other viruses—namely, adenoviruses and cytomegalovirus.”
“The novel contribution of this study is that we have targeted additional viruses, the BK virus and the HHV-6 virus, which had not been targeted this way before,” added study author Bilal Omer, MD, of Baylor College of Medicine.
“This is important because the BK virus does not have an effective treatment, and the complications are significant, including severe pain and bleeding. These patients are in the hospital for weeks, months sometimes, and, now, we have a treatment option.”
The researchers tested their VSTs in a phase 2 trial of 38 HSCT recipients with at least 1 of the aforementioned viruses.
“[To prepare the VSTs,] we take blood from healthy donors who have already been exposed to these viruses and who we have confirmed have immune cells that can fight the infections,” Dr Tzannou said.
“We isolate the cells and let them multiply in culture. The final product is a mixture of cells that, together, can target all 5 viruses. We prepared 59 sets of virus-specific cells from different donors following this procedure.”
“Our strategy is to prepare a number of sets of virus-specific cells ahead of time and store them in a freezer, ready to use when a patient needs them,” Dr Omer noted. “To match patient and donor, we use elaborate matching algorithms.”
Patients
The trial included 38 patients who had undergone HSCT to treat acute myeloid leukemia/myelodysplastic syndromes (n=20), acute lymphoblastic leukemia (n=9), lymphoma/myeloma (n=3), or nonmalignant disorders (n=6).
These 38 patients had a total of 45 infections—CMV (n=17), EBV (n=2), AdV (n=7), BKV (n=16), and HHV-6 (n=3).
Response
The researchers monitored virus levels and other clinical responses in the 37 evaluable patients.
Six weeks after the first VST infusion, the overall response rate was 91.9%.
Seventeen patients received VSTs for persistent CMV. Sixteen of these patients (94.1%) responded, 6 with complete responses (CRs) and 10 with partial responses (PRs).
Two patients received VSTs for EBV, and both achieved a virologic CR.
Seven patients received VSTs for persistent AdV. The response rate was 71.4%. Four patients achieved a CR, 1 had a PR, and 2 patients did not respond.
Three patients received VSTs to treat HHV-6 reactivations. The response rate was 67%. Two patients had a PR, and 1 was not evaluable.
Sixteen patients received VSTs for BKV-associated hemorrhagic cystitis (n= 14) or BKV-associated nephritis (n=2).
All 16 patients responded. One had a clinical and virologic CR. Six had a clinical CR but a virologic PR. Seven had a virologic and clinical PR. And 2 patients had only a virologic PR.
A total of 15 patients received a second VST infusion—1 due to lack of response, 7 who had a PR, and 7 due to recurrence. Ten of these patients responded to the second infusion—1 with a CR and 9 with a PR.
Four patients received a third infusion of VSTs. Two achieved a CR, 1 had a PR, and 1 did not respond.
Toxicity
One patient developed an isolated fever within 24 hours of VST infusion, but the researchers did not observe any other immediate toxicities.
One of the patients with BKV-associated hemorrhagic cystitis experienced transient hydronephrosis and a decrease in renal function associated with a concomitant bacterial urinary tract infection.
Nineteen patients had prior grade 2 to 4 graft-versus-host disease (GVHD)—15 with grade 2 and 4 with grade 3. All GVHD was quiescent at the time of VST infusion.
One patient developed recurrent grade 3 gastrointestinal GVHD after VST infusion and rapid corticosteroid taper. Five patients developed recurrent (n=3) or de novo (n=2) grade 1 to 2 skin GVHD, which resolved with topical treatment (n=4) and reinitiation of corticosteroid treatment (n=1).
Two patients had a flare of upper-gastrointestinal GVHD, which resolved after a brief corticosteroid course.
“We didn’t have any significant toxicities,” Dr Tzannou said. “Taken together, the results of this trial suggest that it is reasonable to consider this treatment as an early option for these patients. We hope that the results of a future multicenter, phase 3 clinical trial will help raise awareness in both physicians and patients that this treatment, which is safe and effective, is available.”
New research suggests virus-specific T cells (VSTs) can protect patients from severe viral infections that sometimes occur after hematopoietic stem cell transplant (HSCT).
The VSTs proved effective against 5 different viruses—Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6).
Ifigeneia Tzannou, MD, of Baylor College of Medicine in Houston, Texas, and her colleagues reported these findings in the Journal of Clinical Oncology.
“In this study, we continued our previous work . . . in which we showed that patients who had developed an Epstein-Barr virus infection after a transplant . . . could be helped by receiving immune cells specialized in eliminating that particular virus,” Dr Tzannou said. “Then, we and others successfully targeted other viruses—namely, adenoviruses and cytomegalovirus.”
“The novel contribution of this study is that we have targeted additional viruses, the BK virus and the HHV-6 virus, which had not been targeted this way before,” added study author Bilal Omer, MD, of Baylor College of Medicine.
“This is important because the BK virus does not have an effective treatment, and the complications are significant, including severe pain and bleeding. These patients are in the hospital for weeks, months sometimes, and, now, we have a treatment option.”
The researchers tested their VSTs in a phase 2 trial of 38 HSCT recipients with at least 1 of the aforementioned viruses.
“[To prepare the VSTs,] we take blood from healthy donors who have already been exposed to these viruses and who we have confirmed have immune cells that can fight the infections,” Dr Tzannou said.
“We isolate the cells and let them multiply in culture. The final product is a mixture of cells that, together, can target all 5 viruses. We prepared 59 sets of virus-specific cells from different donors following this procedure.”
“Our strategy is to prepare a number of sets of virus-specific cells ahead of time and store them in a freezer, ready to use when a patient needs them,” Dr Omer noted. “To match patient and donor, we use elaborate matching algorithms.”
Patients
The trial included 38 patients who had undergone HSCT to treat acute myeloid leukemia/myelodysplastic syndromes (n=20), acute lymphoblastic leukemia (n=9), lymphoma/myeloma (n=3), or nonmalignant disorders (n=6).
These 38 patients had a total of 45 infections—CMV (n=17), EBV (n=2), AdV (n=7), BKV (n=16), and HHV-6 (n=3).
Response
The researchers monitored virus levels and other clinical responses in the 37 evaluable patients.
Six weeks after the first VST infusion, the overall response rate was 91.9%.
Seventeen patients received VSTs for persistent CMV. Sixteen of these patients (94.1%) responded, 6 with complete responses (CRs) and 10 with partial responses (PRs).
Two patients received VSTs for EBV, and both achieved a virologic CR.
Seven patients received VSTs for persistent AdV. The response rate was 71.4%. Four patients achieved a CR, 1 had a PR, and 2 patients did not respond.
Three patients received VSTs to treat HHV-6 reactivations. The response rate was 67%. Two patients had a PR, and 1 was not evaluable.
Sixteen patients received VSTs for BKV-associated hemorrhagic cystitis (n= 14) or BKV-associated nephritis (n=2).
All 16 patients responded. One had a clinical and virologic CR. Six had a clinical CR but a virologic PR. Seven had a virologic and clinical PR. And 2 patients had only a virologic PR.
A total of 15 patients received a second VST infusion—1 due to lack of response, 7 who had a PR, and 7 due to recurrence. Ten of these patients responded to the second infusion—1 with a CR and 9 with a PR.
Four patients received a third infusion of VSTs. Two achieved a CR, 1 had a PR, and 1 did not respond.
Toxicity
One patient developed an isolated fever within 24 hours of VST infusion, but the researchers did not observe any other immediate toxicities.
One of the patients with BKV-associated hemorrhagic cystitis experienced transient hydronephrosis and a decrease in renal function associated with a concomitant bacterial urinary tract infection.
Nineteen patients had prior grade 2 to 4 graft-versus-host disease (GVHD)—15 with grade 2 and 4 with grade 3. All GVHD was quiescent at the time of VST infusion.
One patient developed recurrent grade 3 gastrointestinal GVHD after VST infusion and rapid corticosteroid taper. Five patients developed recurrent (n=3) or de novo (n=2) grade 1 to 2 skin GVHD, which resolved with topical treatment (n=4) and reinitiation of corticosteroid treatment (n=1).
Two patients had a flare of upper-gastrointestinal GVHD, which resolved after a brief corticosteroid course.
“We didn’t have any significant toxicities,” Dr Tzannou said. “Taken together, the results of this trial suggest that it is reasonable to consider this treatment as an early option for these patients. We hope that the results of a future multicenter, phase 3 clinical trial will help raise awareness in both physicians and patients that this treatment, which is safe and effective, is available.”
Tests can produce confusing results after HSCT in MM
Tests used to assess treatment response in multiple myeloma (MM) may often produce confusing results after patients have undergone hematopoietic stem cell transplant (HSCT), a new study suggests.
The tests—serum protein electrophoresis/serum immunofixation electrophoresis (SPEP/SIFE) and serum free light chain assay (SFLCA)—can sometimes produce an oligoclonal pattern that can be mistaken for an M spike and suggest disease recurrence.
The study showed that this confusing result was significantly more likely to occur after patients underwent HSCT than after they received chemotherapy.
Gurmukh Singh, MD, PhD, of Augusta University in Augusta, Georgia, reported these findings in the Journal of Clinical Medicine Research.
For this study, Dr Singh looked at lab and clinical data on 251 MM patients treated from January 2010 to December 2016. One hundred and fifty-nine of those patients received autologous HSCTs.
Dr Singh compared results of SPEP/SIFE and/or SFLCA in patients who underwent HSCT and patients who did not. Each patient had at least 3 tests, and, for HSCT recipients, at least 2 of the tests occurred after transplant.
The incidence of oligoclonal patterns was significantly higher in HSCT recipients than in patients who had chemotherapy alone—57.9% and 8.8%, respectively (P=0.000003).
Only 5 of the 159 HSCT recipients had an oligoclonal pattern before treatment, but 92 of them had one afterward.
More than half of the oligoclonal patterns developed within the first year of HSCT. The earliest pattern was detected at 2 months—as soon as the first post-transplant tests were done—and a few occurred as late as 5 years later.
“We want to emphasize that oligoclonal bands should mostly be recognized as a response to treatment and not be mistaken as a recurrence of the original tumor,” Dr Singh said.
He explained that the key clarifier appears to be the location of the M spike when the diagnosis is made compared to the location of new spikes that may show up after HSCT.
“If the original peak was at location A, now the peak is location B, that allows us to determine that it is not the same abnormal, malignant antibody,” he said. “If it’s in a different location, it’s not the same protein. [T]his is just a normal response of recovery of the bone marrow that could be mistaken for recurrence of the disease.”
Tests used to assess treatment response in multiple myeloma (MM) may often produce confusing results after patients have undergone hematopoietic stem cell transplant (HSCT), a new study suggests.
The tests—serum protein electrophoresis/serum immunofixation electrophoresis (SPEP/SIFE) and serum free light chain assay (SFLCA)—can sometimes produce an oligoclonal pattern that can be mistaken for an M spike and suggest disease recurrence.
The study showed that this confusing result was significantly more likely to occur after patients underwent HSCT than after they received chemotherapy.
Gurmukh Singh, MD, PhD, of Augusta University in Augusta, Georgia, reported these findings in the Journal of Clinical Medicine Research.
For this study, Dr Singh looked at lab and clinical data on 251 MM patients treated from January 2010 to December 2016. One hundred and fifty-nine of those patients received autologous HSCTs.
Dr Singh compared results of SPEP/SIFE and/or SFLCA in patients who underwent HSCT and patients who did not. Each patient had at least 3 tests, and, for HSCT recipients, at least 2 of the tests occurred after transplant.
The incidence of oligoclonal patterns was significantly higher in HSCT recipients than in patients who had chemotherapy alone—57.9% and 8.8%, respectively (P=0.000003).
Only 5 of the 159 HSCT recipients had an oligoclonal pattern before treatment, but 92 of them had one afterward.
More than half of the oligoclonal patterns developed within the first year of HSCT. The earliest pattern was detected at 2 months—as soon as the first post-transplant tests were done—and a few occurred as late as 5 years later.
“We want to emphasize that oligoclonal bands should mostly be recognized as a response to treatment and not be mistaken as a recurrence of the original tumor,” Dr Singh said.
He explained that the key clarifier appears to be the location of the M spike when the diagnosis is made compared to the location of new spikes that may show up after HSCT.
“If the original peak was at location A, now the peak is location B, that allows us to determine that it is not the same abnormal, malignant antibody,” he said. “If it’s in a different location, it’s not the same protein. [T]his is just a normal response of recovery of the bone marrow that could be mistaken for recurrence of the disease.”
Tests used to assess treatment response in multiple myeloma (MM) may often produce confusing results after patients have undergone hematopoietic stem cell transplant (HSCT), a new study suggests.
The tests—serum protein electrophoresis/serum immunofixation electrophoresis (SPEP/SIFE) and serum free light chain assay (SFLCA)—can sometimes produce an oligoclonal pattern that can be mistaken for an M spike and suggest disease recurrence.
The study showed that this confusing result was significantly more likely to occur after patients underwent HSCT than after they received chemotherapy.
Gurmukh Singh, MD, PhD, of Augusta University in Augusta, Georgia, reported these findings in the Journal of Clinical Medicine Research.
For this study, Dr Singh looked at lab and clinical data on 251 MM patients treated from January 2010 to December 2016. One hundred and fifty-nine of those patients received autologous HSCTs.
Dr Singh compared results of SPEP/SIFE and/or SFLCA in patients who underwent HSCT and patients who did not. Each patient had at least 3 tests, and, for HSCT recipients, at least 2 of the tests occurred after transplant.
The incidence of oligoclonal patterns was significantly higher in HSCT recipients than in patients who had chemotherapy alone—57.9% and 8.8%, respectively (P=0.000003).
Only 5 of the 159 HSCT recipients had an oligoclonal pattern before treatment, but 92 of them had one afterward.
More than half of the oligoclonal patterns developed within the first year of HSCT. The earliest pattern was detected at 2 months—as soon as the first post-transplant tests were done—and a few occurred as late as 5 years later.
“We want to emphasize that oligoclonal bands should mostly be recognized as a response to treatment and not be mistaken as a recurrence of the original tumor,” Dr Singh said.
He explained that the key clarifier appears to be the location of the M spike when the diagnosis is made compared to the location of new spikes that may show up after HSCT.
“If the original peak was at location A, now the peak is location B, that allows us to determine that it is not the same abnormal, malignant antibody,” he said. “If it’s in a different location, it’s not the same protein. [T]his is just a normal response of recovery of the bone marrow that could be mistaken for recurrence of the disease.”
Drug receives orphan designation for ocular GVHD
The US Food and Drug Administration (FDA) has granted orphan drug designation to OCU300 (brimonidine tartrate) for the treatment of ocular graft-versus-host disease (oGVHD) occurring after allogeneic hematopoietic stem cell transplant.
Brimonidine tartrate is an alpha adrenergic agonist that is already FDA-approved to lower intraocular pressure in patients with open-angle glaucoma or ocular hypertension.
Ocugen Inc. is repurposing the drug as OCU300 for the treatment of oGVHD under the FDA’s 505(b)(2) regulatory pathway.
“We are very excited to receive the first-ever orphan drug designation by the FDA for oGVHD, emphasizing the unmet medical need for patients with this disease,” said Shankar Musunuri, PhD, chairman, chief executive officer, and co-founder of Ocugen Inc.
“This is a significant milestone that will allow us to further advance the clinical development of OCU300, with a proprietary nanoemulsion, into a phase 3 clinical trial in the near future.”
According to Ocugen, OCU300 produced a beneficial effect in 90% of patients with oGVHD in an observational study, and the drug did not produce significant side effects.
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to OCU300 (brimonidine tartrate) for the treatment of ocular graft-versus-host disease (oGVHD) occurring after allogeneic hematopoietic stem cell transplant.
Brimonidine tartrate is an alpha adrenergic agonist that is already FDA-approved to lower intraocular pressure in patients with open-angle glaucoma or ocular hypertension.
Ocugen Inc. is repurposing the drug as OCU300 for the treatment of oGVHD under the FDA’s 505(b)(2) regulatory pathway.
“We are very excited to receive the first-ever orphan drug designation by the FDA for oGVHD, emphasizing the unmet medical need for patients with this disease,” said Shankar Musunuri, PhD, chairman, chief executive officer, and co-founder of Ocugen Inc.
“This is a significant milestone that will allow us to further advance the clinical development of OCU300, with a proprietary nanoemulsion, into a phase 3 clinical trial in the near future.”
According to Ocugen, OCU300 produced a beneficial effect in 90% of patients with oGVHD in an observational study, and the drug did not produce significant side effects.
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to OCU300 (brimonidine tartrate) for the treatment of ocular graft-versus-host disease (oGVHD) occurring after allogeneic hematopoietic stem cell transplant.
Brimonidine tartrate is an alpha adrenergic agonist that is already FDA-approved to lower intraocular pressure in patients with open-angle glaucoma or ocular hypertension.
Ocugen Inc. is repurposing the drug as OCU300 for the treatment of oGVHD under the FDA’s 505(b)(2) regulatory pathway.
“We are very excited to receive the first-ever orphan drug designation by the FDA for oGVHD, emphasizing the unmet medical need for patients with this disease,” said Shankar Musunuri, PhD, chairman, chief executive officer, and co-founder of Ocugen Inc.
“This is a significant milestone that will allow us to further advance the clinical development of OCU300, with a proprietary nanoemulsion, into a phase 3 clinical trial in the near future.”
According to Ocugen, OCU300 produced a beneficial effect in 90% of patients with oGVHD in an observational study, and the drug did not produce significant side effects.
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
Program reduces transfusions in leukemia, HSCT patients
New research suggests a patient blood management (PBM) program can safely reduce transfusion use in patients with acute leukemia and those undergoing hematopoietic stem cell transplant (HSCT).
The program significantly reduced the use of red blood cell (RBC) and platelet transfusions without increasing morbidity or mortality in patients who were receiving intensive chemotherapy to treat acute leukemia and in patients receiving an allogeneic or autologous HSCT.
“There has been a long-standing belief among hematologists that patients with leukemia undergoing chemotherapy should have a transfusion of red blood cells if their hemoglobin level drops below about 9 g/dL to help avoid adverse outcomes,” said study author Michael Leahy, MB ChB, a consultant hematologist at the University of Western Australia in Perth.
“Findings in this real-world, non-clinical trial setting challenge that belief.”
Dr Leahy and his colleagues published their findings in Transfusion.
The researchers said the PBM program used in this study was built around the “3 pillars” concept of PBM, which are:
- Optimize the patient’s RBC mass
- Minimize blood loss
- Harness and optimize the patient’s physiologic anemia reserve.
No specific transfusion thresholds were established. However, the hospitals did adopt a single-unit RBC transfusion policy for symptomatic anemic patients who were not actively bleeding.
Results
The study included 695 admissions to 2 major hospitals in Western Australia. Patients were admitted between July 2010 and December 2014 for treatment of acute leukemia or for autologous or allogeneic HSCT.
During this time, the patients received 3384 RBC units and 3639 units of platelets.
The mean number of platelet units transfused per hospital admission decreased 35% from baseline to the end of the study period, from 6.3 to 4.1 units (P<0.001).
The mean number of RBC units transfused decreased 39%, from 6.1 to 3.7 (P<0.001). Meanwhile, the use of single-unit RBC transfusions increased from 39% to 67% (P<0.001).
And the mean hemoglobin level prior to RBC transfusion decreased from 8.0 g/dL to 6.8 g/dL (P<0.001).
“This study suggests that patients undergoing chemotherapy with hematological disease may tolerate much lower levels of hemoglobin than previously thought,” said Shannon Farmer, an adjunct research fellow at the University of Western Australia.
“The transfusion threshold, the hemoglobin value at which a transfusion is given, dropped significantly from 8.0 g/dL at the beginning of the study to 6.8 g/dL at the end. This was associated with significant reductions in transfusion and substantial costs savings without evidence of harm to the patients. In fact, it was associated with a trend toward improved survival.”
The reduction in blood products over the study period resulted in a cost savings of AU$694,886 (US$654,007)—AU$389,537 (US$364,177) for RBCs and AU$305,349 (US$289,830) for platelets.
There were no significant changes over the study period in length of hospital stay, serious bleeding events, or in-hospital mortality.
There was a non-significant reduction in the mean length of hospital stay, from 24.5 days to 22.6 days (P=0.338). The difference was still not significant after the researchers adjusted for patient age, patient group, and comorbidities (incident rate ratio=0.88; 95% CI, 0.75-1.04).
The rate of serious bleeding increased over the study period, from 5.3% to 7.0% (P=0.582). After adjustment, the odds ratio was 1.14 (95% CI, 0.38-3.44; P=0.811).
There was a non-significant decrease in in-hospital mortality, from 5.3% to 2.0% (P=0.218). After adjustment, the odds ratio was 0.31 (95% CI, 0.06-1.56; P=0.154).
Based on these results, the researchers concluded that PBM programs could have a substantial impact in this patient population, reducing blood utilization and healthcare costs.
New research suggests a patient blood management (PBM) program can safely reduce transfusion use in patients with acute leukemia and those undergoing hematopoietic stem cell transplant (HSCT).
The program significantly reduced the use of red blood cell (RBC) and platelet transfusions without increasing morbidity or mortality in patients who were receiving intensive chemotherapy to treat acute leukemia and in patients receiving an allogeneic or autologous HSCT.
“There has been a long-standing belief among hematologists that patients with leukemia undergoing chemotherapy should have a transfusion of red blood cells if their hemoglobin level drops below about 9 g/dL to help avoid adverse outcomes,” said study author Michael Leahy, MB ChB, a consultant hematologist at the University of Western Australia in Perth.
“Findings in this real-world, non-clinical trial setting challenge that belief.”
Dr Leahy and his colleagues published their findings in Transfusion.
The researchers said the PBM program used in this study was built around the “3 pillars” concept of PBM, which are:
- Optimize the patient’s RBC mass
- Minimize blood loss
- Harness and optimize the patient’s physiologic anemia reserve.
No specific transfusion thresholds were established. However, the hospitals did adopt a single-unit RBC transfusion policy for symptomatic anemic patients who were not actively bleeding.
Results
The study included 695 admissions to 2 major hospitals in Western Australia. Patients were admitted between July 2010 and December 2014 for treatment of acute leukemia or for autologous or allogeneic HSCT.
During this time, the patients received 3384 RBC units and 3639 units of platelets.
The mean number of platelet units transfused per hospital admission decreased 35% from baseline to the end of the study period, from 6.3 to 4.1 units (P<0.001).
The mean number of RBC units transfused decreased 39%, from 6.1 to 3.7 (P<0.001). Meanwhile, the use of single-unit RBC transfusions increased from 39% to 67% (P<0.001).
And the mean hemoglobin level prior to RBC transfusion decreased from 8.0 g/dL to 6.8 g/dL (P<0.001).
“This study suggests that patients undergoing chemotherapy with hematological disease may tolerate much lower levels of hemoglobin than previously thought,” said Shannon Farmer, an adjunct research fellow at the University of Western Australia.
“The transfusion threshold, the hemoglobin value at which a transfusion is given, dropped significantly from 8.0 g/dL at the beginning of the study to 6.8 g/dL at the end. This was associated with significant reductions in transfusion and substantial costs savings without evidence of harm to the patients. In fact, it was associated with a trend toward improved survival.”
The reduction in blood products over the study period resulted in a cost savings of AU$694,886 (US$654,007)—AU$389,537 (US$364,177) for RBCs and AU$305,349 (US$289,830) for platelets.
There were no significant changes over the study period in length of hospital stay, serious bleeding events, or in-hospital mortality.
There was a non-significant reduction in the mean length of hospital stay, from 24.5 days to 22.6 days (P=0.338). The difference was still not significant after the researchers adjusted for patient age, patient group, and comorbidities (incident rate ratio=0.88; 95% CI, 0.75-1.04).
The rate of serious bleeding increased over the study period, from 5.3% to 7.0% (P=0.582). After adjustment, the odds ratio was 1.14 (95% CI, 0.38-3.44; P=0.811).
There was a non-significant decrease in in-hospital mortality, from 5.3% to 2.0% (P=0.218). After adjustment, the odds ratio was 0.31 (95% CI, 0.06-1.56; P=0.154).
Based on these results, the researchers concluded that PBM programs could have a substantial impact in this patient population, reducing blood utilization and healthcare costs.
New research suggests a patient blood management (PBM) program can safely reduce transfusion use in patients with acute leukemia and those undergoing hematopoietic stem cell transplant (HSCT).
The program significantly reduced the use of red blood cell (RBC) and platelet transfusions without increasing morbidity or mortality in patients who were receiving intensive chemotherapy to treat acute leukemia and in patients receiving an allogeneic or autologous HSCT.
“There has been a long-standing belief among hematologists that patients with leukemia undergoing chemotherapy should have a transfusion of red blood cells if their hemoglobin level drops below about 9 g/dL to help avoid adverse outcomes,” said study author Michael Leahy, MB ChB, a consultant hematologist at the University of Western Australia in Perth.
“Findings in this real-world, non-clinical trial setting challenge that belief.”
Dr Leahy and his colleagues published their findings in Transfusion.
The researchers said the PBM program used in this study was built around the “3 pillars” concept of PBM, which are:
- Optimize the patient’s RBC mass
- Minimize blood loss
- Harness and optimize the patient’s physiologic anemia reserve.
No specific transfusion thresholds were established. However, the hospitals did adopt a single-unit RBC transfusion policy for symptomatic anemic patients who were not actively bleeding.
Results
The study included 695 admissions to 2 major hospitals in Western Australia. Patients were admitted between July 2010 and December 2014 for treatment of acute leukemia or for autologous or allogeneic HSCT.
During this time, the patients received 3384 RBC units and 3639 units of platelets.
The mean number of platelet units transfused per hospital admission decreased 35% from baseline to the end of the study period, from 6.3 to 4.1 units (P<0.001).
The mean number of RBC units transfused decreased 39%, from 6.1 to 3.7 (P<0.001). Meanwhile, the use of single-unit RBC transfusions increased from 39% to 67% (P<0.001).
And the mean hemoglobin level prior to RBC transfusion decreased from 8.0 g/dL to 6.8 g/dL (P<0.001).
“This study suggests that patients undergoing chemotherapy with hematological disease may tolerate much lower levels of hemoglobin than previously thought,” said Shannon Farmer, an adjunct research fellow at the University of Western Australia.
“The transfusion threshold, the hemoglobin value at which a transfusion is given, dropped significantly from 8.0 g/dL at the beginning of the study to 6.8 g/dL at the end. This was associated with significant reductions in transfusion and substantial costs savings without evidence of harm to the patients. In fact, it was associated with a trend toward improved survival.”
The reduction in blood products over the study period resulted in a cost savings of AU$694,886 (US$654,007)—AU$389,537 (US$364,177) for RBCs and AU$305,349 (US$289,830) for platelets.
There were no significant changes over the study period in length of hospital stay, serious bleeding events, or in-hospital mortality.
There was a non-significant reduction in the mean length of hospital stay, from 24.5 days to 22.6 days (P=0.338). The difference was still not significant after the researchers adjusted for patient age, patient group, and comorbidities (incident rate ratio=0.88; 95% CI, 0.75-1.04).
The rate of serious bleeding increased over the study period, from 5.3% to 7.0% (P=0.582). After adjustment, the odds ratio was 1.14 (95% CI, 0.38-3.44; P=0.811).
There was a non-significant decrease in in-hospital mortality, from 5.3% to 2.0% (P=0.218). After adjustment, the odds ratio was 0.31 (95% CI, 0.06-1.56; P=0.154).
Based on these results, the researchers concluded that PBM programs could have a substantial impact in this patient population, reducing blood utilization and healthcare costs.
FDA approves first treatment for cGVHD
The US Food and Drug Administration (FDA) has expanded the approved use of ibrutinib (Imbruvica) to include the treatment of adults with chronic graft-versus-host disease (cGVHD) who have failed at least one prior treatment.
This makes ibrutinib the first FDA-approved therapy for cGVHD.
Ibrutinib was previously FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström’s macroglobulinemia, marginal zone lymphoma, and mantle cell lymphoma.
“This approval highlights how a known treatment for cancer is finding a new use in treating a serious and life-threatening condition that may occur in patients with blood cancer who receive a stem cell transplant,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
The approval of ibrutinib to treat cGVHD is based on results of a phase 2 trial, which were presented at the 2016 ASH Annual Meeting.
The trial included 42 patients with cGVHD whose symptoms persisted despite standard treatment with corticosteroids. Most patients’ symptoms included mouth ulcers and skin rashes, and more than 50% had 2 or more organs affected by cGVHD.
Sixty-seven percent of patients responded to treatment with ibrutinib, experiencing improvements in their cGVHD symptoms. In 48% of patients, this improvement lasted for 5 months or longer.
Common side effects of ibrutinib in this trial were fatigue, bruising, diarrhea, thrombocytopenia, muscle spasms, swelling and stomatitis, nausea, hemorrhage, anemia, and pneumonia.
The US Food and Drug Administration (FDA) has expanded the approved use of ibrutinib (Imbruvica) to include the treatment of adults with chronic graft-versus-host disease (cGVHD) who have failed at least one prior treatment.
This makes ibrutinib the first FDA-approved therapy for cGVHD.
Ibrutinib was previously FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström’s macroglobulinemia, marginal zone lymphoma, and mantle cell lymphoma.
“This approval highlights how a known treatment for cancer is finding a new use in treating a serious and life-threatening condition that may occur in patients with blood cancer who receive a stem cell transplant,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
The approval of ibrutinib to treat cGVHD is based on results of a phase 2 trial, which were presented at the 2016 ASH Annual Meeting.
The trial included 42 patients with cGVHD whose symptoms persisted despite standard treatment with corticosteroids. Most patients’ symptoms included mouth ulcers and skin rashes, and more than 50% had 2 or more organs affected by cGVHD.
Sixty-seven percent of patients responded to treatment with ibrutinib, experiencing improvements in their cGVHD symptoms. In 48% of patients, this improvement lasted for 5 months or longer.
Common side effects of ibrutinib in this trial were fatigue, bruising, diarrhea, thrombocytopenia, muscle spasms, swelling and stomatitis, nausea, hemorrhage, anemia, and pneumonia.
The US Food and Drug Administration (FDA) has expanded the approved use of ibrutinib (Imbruvica) to include the treatment of adults with chronic graft-versus-host disease (cGVHD) who have failed at least one prior treatment.
This makes ibrutinib the first FDA-approved therapy for cGVHD.
Ibrutinib was previously FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström’s macroglobulinemia, marginal zone lymphoma, and mantle cell lymphoma.
“This approval highlights how a known treatment for cancer is finding a new use in treating a serious and life-threatening condition that may occur in patients with blood cancer who receive a stem cell transplant,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
The approval of ibrutinib to treat cGVHD is based on results of a phase 2 trial, which were presented at the 2016 ASH Annual Meeting.
The trial included 42 patients with cGVHD whose symptoms persisted despite standard treatment with corticosteroids. Most patients’ symptoms included mouth ulcers and skin rashes, and more than 50% had 2 or more organs affected by cGVHD.
Sixty-seven percent of patients responded to treatment with ibrutinib, experiencing improvements in their cGVHD symptoms. In 48% of patients, this improvement lasted for 5 months or longer.
Common side effects of ibrutinib in this trial were fatigue, bruising, diarrhea, thrombocytopenia, muscle spasms, swelling and stomatitis, nausea, hemorrhage, anemia, and pneumonia.
T-cell product improves outcomes of haplo-HSCT
MADRID—Updated results of a phase 1/2 study suggest the T-cell product BPX-501 lowers the risks associated with haploidentical hematopoietic stem cell transplant (haplo-HSCT).
In this ongoing study, researchers are testing BPX-501 in pediatric patients undergoing haplo-HSCT to treat a range of hematologic disorders.
Patients treated thus far have experienced rapid engraftment and early hospital discharge, a low rate of acute graft-versus-host disease (GHVD), no extensive chronic GVHD, and a low rate of transplant-related mortality at 180 days.
“The combination of haploidentical transplantation and BPX-501 infusion is an effective strategy for children in need of an allograft lacking a compatible donor,” said study investigator Mattia Algeri, MD, of Ospedale Pediatrico Bambino Gesù in Rome, Italy.
Dr Algeri presented these results during the Presidential Symposium at the 22nd Congress of the European Hematology Association (EHA) as abstract S146.
The research was sponsored by Bellicum Pharmaceuticals, Inc., the company developing BPX-501.
About BPX-501
BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate the T cells in the event of toxicity.
Rimiducid is used to activate the CaspaCIDe safety switch, which consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway.
The goal of this therapy is to allow physicians to more safely perform haplo-HSCTs.
Patients
Dr Algeri and his colleagues have tested BPX-501 in 98 pediatric patients treated at centers in Europe and the US.
Fifty-nine patients had non-malignant conditions, including primary immune deficiency (n=26), thalassemia major (n=8), sickle cell disease (n=5), Diamond-Blackfan anemia (n=2), Swachman-Diamond syndrome (n=1), Fanconi anemia (n=9), hemophagocytic lymphohistiocytosis (n=6), aplastic anemia (n=1), and osteoporosis (n=1).
Thirty-nine patients had malignant conditions, including acute lymphoblastic leukemia (ALL, n=21), acute myeloid leukemia (AML, n=14), myelodysplastic syndromes (MDS, n=3), and non-Hodgkin lymphoma (NHL, n=1).
The patients received BPX-501 after an alpha/beta T-cell-depleted haplo-HSCT. All patients had at least 6 months of follow-up.
Overall results
Ninety-five percent of the patients engrafted (93/98), and the researchers said they observed rapid recovery of T cells, B cells, and immunoglobulins.
At 180 days, the incidence of transplant-related mortality was 5%, and there were no cases of post-transplant lymphoproliferative disorder.
The cumulative incidence of grade 2-4 acute GVHD was 14%. For patients with at least 1 year of follow-up, the cumulative incidence of chronic GVHD at 1 year was 3%.
Eleven patients received rimiducid—10 who had uncontrollable acute GVHD and 1 who developed late acute GVHD. In all of these patients, GVHD resolved and has not recurred.
There were no adverse events associated with BPX-501 or rimiducid.
European cohort
Dr Algeri presented more detailed data on the 61 patients treated at centers in Europe.
Fifteen of these patients had ALL, 10 had AML, 16 had primary immune deficiency, 7 had thalassemia major, 1 had sickle cell disease, 2 had Diamond-Blackfan anemia, 5 had Fanconi anemia, 4 had hemophagocytic lymphohistiocytosis, and 1 had osteoporosis.
Their median age was 4.8 (range, 0.25-17), and 56% were male. The patients received busulfan-based conditioning (41%), total body irradiation (36%), treosulfan-based conditioning (18%), and other conditioning (5%).
Ninety-five percent of the patients had a parent donor, and the other 5% had a sibling donor. The median donor age was 36 (range, 19-50).
The patients’ median time to neutrophil recovery was 15 days (range, 9-75), and their median time to platelet recovery was 10 days (range, 4-64). Their median time to discharge was 25 days (range, 14-122).
The cumulative incidence of acute grade 2-4 GVHD was 9.9%, and the cumulative incidence of acute grade 3-4 GVHD was 3.3%.
There were no cases of transplant-related mortality at 180 days and no cases of extensive chronic GVHD.
“These preliminary data compare favorably to previously published data on matched, unrelated donor transplantation,” Dr Algeri said. “And for this reason, an observational matched, unrelated donor study is being initiated to enable comparison of the safety and efficacy of haploidentical transplantation and BPX-501 infusion to the standard of care for patients without a matched sibling donor.”
MADRID—Updated results of a phase 1/2 study suggest the T-cell product BPX-501 lowers the risks associated with haploidentical hematopoietic stem cell transplant (haplo-HSCT).
In this ongoing study, researchers are testing BPX-501 in pediatric patients undergoing haplo-HSCT to treat a range of hematologic disorders.
Patients treated thus far have experienced rapid engraftment and early hospital discharge, a low rate of acute graft-versus-host disease (GHVD), no extensive chronic GVHD, and a low rate of transplant-related mortality at 180 days.
“The combination of haploidentical transplantation and BPX-501 infusion is an effective strategy for children in need of an allograft lacking a compatible donor,” said study investigator Mattia Algeri, MD, of Ospedale Pediatrico Bambino Gesù in Rome, Italy.
Dr Algeri presented these results during the Presidential Symposium at the 22nd Congress of the European Hematology Association (EHA) as abstract S146.
The research was sponsored by Bellicum Pharmaceuticals, Inc., the company developing BPX-501.
About BPX-501
BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate the T cells in the event of toxicity.
Rimiducid is used to activate the CaspaCIDe safety switch, which consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway.
The goal of this therapy is to allow physicians to more safely perform haplo-HSCTs.
Patients
Dr Algeri and his colleagues have tested BPX-501 in 98 pediatric patients treated at centers in Europe and the US.
Fifty-nine patients had non-malignant conditions, including primary immune deficiency (n=26), thalassemia major (n=8), sickle cell disease (n=5), Diamond-Blackfan anemia (n=2), Swachman-Diamond syndrome (n=1), Fanconi anemia (n=9), hemophagocytic lymphohistiocytosis (n=6), aplastic anemia (n=1), and osteoporosis (n=1).
Thirty-nine patients had malignant conditions, including acute lymphoblastic leukemia (ALL, n=21), acute myeloid leukemia (AML, n=14), myelodysplastic syndromes (MDS, n=3), and non-Hodgkin lymphoma (NHL, n=1).
The patients received BPX-501 after an alpha/beta T-cell-depleted haplo-HSCT. All patients had at least 6 months of follow-up.
Overall results
Ninety-five percent of the patients engrafted (93/98), and the researchers said they observed rapid recovery of T cells, B cells, and immunoglobulins.
At 180 days, the incidence of transplant-related mortality was 5%, and there were no cases of post-transplant lymphoproliferative disorder.
The cumulative incidence of grade 2-4 acute GVHD was 14%. For patients with at least 1 year of follow-up, the cumulative incidence of chronic GVHD at 1 year was 3%.
Eleven patients received rimiducid—10 who had uncontrollable acute GVHD and 1 who developed late acute GVHD. In all of these patients, GVHD resolved and has not recurred.
There were no adverse events associated with BPX-501 or rimiducid.
European cohort
Dr Algeri presented more detailed data on the 61 patients treated at centers in Europe.
Fifteen of these patients had ALL, 10 had AML, 16 had primary immune deficiency, 7 had thalassemia major, 1 had sickle cell disease, 2 had Diamond-Blackfan anemia, 5 had Fanconi anemia, 4 had hemophagocytic lymphohistiocytosis, and 1 had osteoporosis.
Their median age was 4.8 (range, 0.25-17), and 56% were male. The patients received busulfan-based conditioning (41%), total body irradiation (36%), treosulfan-based conditioning (18%), and other conditioning (5%).
Ninety-five percent of the patients had a parent donor, and the other 5% had a sibling donor. The median donor age was 36 (range, 19-50).
The patients’ median time to neutrophil recovery was 15 days (range, 9-75), and their median time to platelet recovery was 10 days (range, 4-64). Their median time to discharge was 25 days (range, 14-122).
The cumulative incidence of acute grade 2-4 GVHD was 9.9%, and the cumulative incidence of acute grade 3-4 GVHD was 3.3%.
There were no cases of transplant-related mortality at 180 days and no cases of extensive chronic GVHD.
“These preliminary data compare favorably to previously published data on matched, unrelated donor transplantation,” Dr Algeri said. “And for this reason, an observational matched, unrelated donor study is being initiated to enable comparison of the safety and efficacy of haploidentical transplantation and BPX-501 infusion to the standard of care for patients without a matched sibling donor.”
MADRID—Updated results of a phase 1/2 study suggest the T-cell product BPX-501 lowers the risks associated with haploidentical hematopoietic stem cell transplant (haplo-HSCT).
In this ongoing study, researchers are testing BPX-501 in pediatric patients undergoing haplo-HSCT to treat a range of hematologic disorders.
Patients treated thus far have experienced rapid engraftment and early hospital discharge, a low rate of acute graft-versus-host disease (GHVD), no extensive chronic GVHD, and a low rate of transplant-related mortality at 180 days.
“The combination of haploidentical transplantation and BPX-501 infusion is an effective strategy for children in need of an allograft lacking a compatible donor,” said study investigator Mattia Algeri, MD, of Ospedale Pediatrico Bambino Gesù in Rome, Italy.
Dr Algeri presented these results during the Presidential Symposium at the 22nd Congress of the European Hematology Association (EHA) as abstract S146.
The research was sponsored by Bellicum Pharmaceuticals, Inc., the company developing BPX-501.
About BPX-501
BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate the T cells in the event of toxicity.
Rimiducid is used to activate the CaspaCIDe safety switch, which consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway.
The goal of this therapy is to allow physicians to more safely perform haplo-HSCTs.
Patients
Dr Algeri and his colleagues have tested BPX-501 in 98 pediatric patients treated at centers in Europe and the US.
Fifty-nine patients had non-malignant conditions, including primary immune deficiency (n=26), thalassemia major (n=8), sickle cell disease (n=5), Diamond-Blackfan anemia (n=2), Swachman-Diamond syndrome (n=1), Fanconi anemia (n=9), hemophagocytic lymphohistiocytosis (n=6), aplastic anemia (n=1), and osteoporosis (n=1).
Thirty-nine patients had malignant conditions, including acute lymphoblastic leukemia (ALL, n=21), acute myeloid leukemia (AML, n=14), myelodysplastic syndromes (MDS, n=3), and non-Hodgkin lymphoma (NHL, n=1).
The patients received BPX-501 after an alpha/beta T-cell-depleted haplo-HSCT. All patients had at least 6 months of follow-up.
Overall results
Ninety-five percent of the patients engrafted (93/98), and the researchers said they observed rapid recovery of T cells, B cells, and immunoglobulins.
At 180 days, the incidence of transplant-related mortality was 5%, and there were no cases of post-transplant lymphoproliferative disorder.
The cumulative incidence of grade 2-4 acute GVHD was 14%. For patients with at least 1 year of follow-up, the cumulative incidence of chronic GVHD at 1 year was 3%.
Eleven patients received rimiducid—10 who had uncontrollable acute GVHD and 1 who developed late acute GVHD. In all of these patients, GVHD resolved and has not recurred.
There were no adverse events associated with BPX-501 or rimiducid.
European cohort
Dr Algeri presented more detailed data on the 61 patients treated at centers in Europe.
Fifteen of these patients had ALL, 10 had AML, 16 had primary immune deficiency, 7 had thalassemia major, 1 had sickle cell disease, 2 had Diamond-Blackfan anemia, 5 had Fanconi anemia, 4 had hemophagocytic lymphohistiocytosis, and 1 had osteoporosis.
Their median age was 4.8 (range, 0.25-17), and 56% were male. The patients received busulfan-based conditioning (41%), total body irradiation (36%), treosulfan-based conditioning (18%), and other conditioning (5%).
Ninety-five percent of the patients had a parent donor, and the other 5% had a sibling donor. The median donor age was 36 (range, 19-50).
The patients’ median time to neutrophil recovery was 15 days (range, 9-75), and their median time to platelet recovery was 10 days (range, 4-64). Their median time to discharge was 25 days (range, 14-122).
The cumulative incidence of acute grade 2-4 GVHD was 9.9%, and the cumulative incidence of acute grade 3-4 GVHD was 3.3%.
There were no cases of transplant-related mortality at 180 days and no cases of extensive chronic GVHD.
“These preliminary data compare favorably to previously published data on matched, unrelated donor transplantation,” Dr Algeri said. “And for this reason, an observational matched, unrelated donor study is being initiated to enable comparison of the safety and efficacy of haploidentical transplantation and BPX-501 infusion to the standard of care for patients without a matched sibling donor.”
Combo with daratumumab could be alternative to ASCT in MM
CHICAGO—Results of an open-label phase 1b study of daratumumab combined with carfilzomib, lenalidomide, and dexamethasone (KRd) in newly diagnosed multiple myeloma (MM) patients have shown the combination to be highly effective, with an overall response rate of 100%.
Ninety-one percent of patients achieved a very good partial response (VGPR) or better, and 43% achieved a complete response (CR) or better.
Investigators had hypothesized that rather than using autologous stem cell transplant (ASCT) to improve results of treatment with KRd, the combination could alternatively be improved by incorporating daratumumab into a KRd regimen.
Andrzej Jakubowiak, MD, of the University of Chicago Medical Center in Illinois, presented the findings of the MMY1001 study at the 2017 ASCO Annual Meeting (abstract 8000*).
“I think what was one of the more important developments in myeloma last year,” Dr Jakubowiak said, “was data from randomized studies showing that adding daratumumab to either lenalidomide and dexamethasone in the POLLUX study or bortezomib and dexamethasone, a proteasome inhibitor, in the CASTOR study, improves responses, depth of response, and . . . dramatically improved progression-free survival.”
“[W]e have now the rationale to potentially combine daratumumab with both an IMiD and proteasome inhibitor,” he explained, “which led to the development of this phase 1b study in which we combined daratumumab with KRd and evaluated tolerability and efficacy.”
Study design
Twenty-two transplant-eligible or -ineligible newly diagnosed MM patients were enrolled on the study.
Treatment duration was planned to be 13 cycles or less and patients had the option to move to transplant after 4 cycles.
They could have no clinically significant cardiac disease and echocardiogram was required prior to transplant.
The dosing schedule was the established dosing schema for daratumumab and KRd with 2 notable differences in the 28-day cycles.
First, the daratumumab dose was a split dose. So patients received 8 mg/kg on days 1-2 of cycle 1, 16 mg/kg a week on cycle 2, 16 mg/kg every 2 weeks on cycles 3 – 6, and every 4th week thereafter.
The second difference was carfilzomib dosing was a weekly regimen with escalation from 20 mg/m2 on day 1, cycle 1 to 70 mg/m2 on day 8 of cycle 1.
Lenalidomide (25 mg on days 1-21 of each cycle) and dexamethasone (40 mg/week) were the standard regimens for these drugs.
The primary endpoint was safety and tolerability. The secondary endpoint was overall response rate (ORR), duration of response, time to response, and infusion-related reactions (IRR).
The study also had an exploratory endpoint of progression-free survival (PFS).
Baseline characteristics
Patients were a median age of 59.5 years (range 34 – 74). About two thirds were younger than 65 and one third were between 65 and 75.
A little over half were male and most (86%) were white.
A little more than half (55%) had an ECOG score of 0, 41% were ECOG 1, and 5% were ECOG 2.
Patient disposition
As of the cutoff date of March 24, 8 of the 22 patients enrolled (36%) discontinued treatment: 1 due to an adverse event (AE), 1 due to progressive disease, and 6 patients (27%) proceeded to ASCT.
Dr Jakubowiak pointed out that response was censored at this point for patients who proceeded to transplant.
The median follow-up was 10.8 months (range, 4.0 – 12.5) and the median number of treatment cycles was 11.5 (range, 1.0 – 13.0).
“What is of interest to many of us,” Dr Jakubowiak said, “is that patients were escalated to the planned dose of 70 mg/m2 by cycle 2 except for 3 patients.”
Of the 3, 1 discontinued before day 1 of the second cycle due to toxicity, 1 had a dose reduction to 56 mg/m2 at day of the second cycle, and 1 escalated to 70 mg/m2 at day 8 of cycle 3.
Ultimately, all patients who remained on study were able to escalate to 70 mg/m2.
Safety
The hematologic treatment-emergent adverse events (TEAE) generally followed what has been observed in similar studies before, Dr Jakubowiak noted.
Hematologic TEAEs of all grades occurring in 30% or more of patients were lymphopenia (68%), thrombocytopenia (55%), anemia (46%), leukopenia (41%), and neutropenia (32%).
The most common non-hematologic TEAEs of all grades occurring in 30% of patients or more were diarrhea (73%), upper respiratory infection (59%) cough, constipation, and fatigue (50% each), dyspnea and insomnia (46%), nausea, rash, and back pain (41%), muscle spasm (36%), and vomiting, pain in extremity, hyperglycemia, and increased ALT (32%).
The most common grade 3/4 TEAEs were infrequent and many events had none of grade 3/4 severity.
The safety profile is consistent with what was previously reported for daratumumab or KRd, Dr Jakubowiak affirmed.
Serious TEAEs
Serious TEAEs occurred in 10 patients (46%), with many occurring in just 1 patient. Pulmonary embolism (PE) was the most frequent, occurring in 3 patients.
All patients were required to be on aspirin prophylaxis and 1 of the patients who had a PE discontinued therapy.
The number of patients with a serious TEAE reasonably related to an individual study drug were 3 (14%) for daratumumab, 5 (23%) for carfilzomib, 5 (23%) for lenalidomide, and 2 (9%) for dexamethasone.
The TEAEs of interest—tachycardia, congestive heart failure, and hypertension—occurred in a single patient each.
Overall, serious TEAEs were consistent with previous reports from KRd studies.
Echocardiogram assessment
Investigators conducted 30 systemic evaluations on the impact of this regimen on heart function. The investigators observed no change from baseline through the duration of treatment in patients’ left ventricular ejection fractions.
One patient developed congestive heart failure, possibly related to daratumumab or carfilzomib. This patient resumed treatment with a reduced carfilzomib dose, elected ASCT on study day 113, and ended treatment with a VGPR.
“In all,” Dr Jakubowiak said, “we feel that there is no apparent signal of adverse impact of the addition of daratumumab on cardiac function.”
Infusion times and reactions
Overall, IRRs occurred in 27% of the patients, “which appears lower than with previous daratumumab studies,” Dr Jakubowiak noted. And IRRs occurred more frequently during the first infusion than subsequent infusions.
The split-dose infusion time was very similar to that of second and subsequent cycles.
There were limited events related to infusions. All were grade 1 or 2 and most occurred in only a single patient.
Response rate
The median number of treatment cycles administered was 11.5 (range, 2.0 – 13.0). The best response was 100% PR or better, 91% achieved VGPR or better, 42% CR or better, and 29% a stringent CR.
The depth of response improved with duration of treatment. For example, the sCR rate increased from 5% after 4 cycles to 29% at the end of treatment.
PFS was an exploratory endpoint. One patient progressed at 10.8 months and the 12-month PFS rate was 94% with all patients alive.
Stem cell harvest and ASCT
“For many of us,” Dr Jakubowiak commented, “it’s also of interest how this regimen will impact stem cell harvest.”
Nineteen of 22 patients were deemed to be transplant eligible, and the median number of CD34+ cells collected from them was 10.4 x 106 cells/kg.
Patients had a median of 5 treatment cycles prior to stem cell harvest, and 14 (74%) had a VGPR or better prior to harvest.
The investigators believe stem cell yield was consistent with previous KRd studies.
Dr Jakubowiak commented that the deepening of response over time “is a phenomenon we think is important. . . . In all, the data from this small phase 1b study provide support for further evaluation of this regimen in newly diagnosed myeloma."
The study was funded by Janssen Research and Development, LLC. 
*Data presented during the meeting differ from the abstract.
CHICAGO—Results of an open-label phase 1b study of daratumumab combined with carfilzomib, lenalidomide, and dexamethasone (KRd) in newly diagnosed multiple myeloma (MM) patients have shown the combination to be highly effective, with an overall response rate of 100%.
Ninety-one percent of patients achieved a very good partial response (VGPR) or better, and 43% achieved a complete response (CR) or better.
Investigators had hypothesized that rather than using autologous stem cell transplant (ASCT) to improve results of treatment with KRd, the combination could alternatively be improved by incorporating daratumumab into a KRd regimen.
Andrzej Jakubowiak, MD, of the University of Chicago Medical Center in Illinois, presented the findings of the MMY1001 study at the 2017 ASCO Annual Meeting (abstract 8000*).
“I think what was one of the more important developments in myeloma last year,” Dr Jakubowiak said, “was data from randomized studies showing that adding daratumumab to either lenalidomide and dexamethasone in the POLLUX study or bortezomib and dexamethasone, a proteasome inhibitor, in the CASTOR study, improves responses, depth of response, and . . . dramatically improved progression-free survival.”
“[W]e have now the rationale to potentially combine daratumumab with both an IMiD and proteasome inhibitor,” he explained, “which led to the development of this phase 1b study in which we combined daratumumab with KRd and evaluated tolerability and efficacy.”
Study design
Twenty-two transplant-eligible or -ineligible newly diagnosed MM patients were enrolled on the study.
Treatment duration was planned to be 13 cycles or less and patients had the option to move to transplant after 4 cycles.
They could have no clinically significant cardiac disease and echocardiogram was required prior to transplant.
The dosing schedule was the established dosing schema for daratumumab and KRd with 2 notable differences in the 28-day cycles.
First, the daratumumab dose was a split dose. So patients received 8 mg/kg on days 1-2 of cycle 1, 16 mg/kg a week on cycle 2, 16 mg/kg every 2 weeks on cycles 3 – 6, and every 4th week thereafter.
The second difference was carfilzomib dosing was a weekly regimen with escalation from 20 mg/m2 on day 1, cycle 1 to 70 mg/m2 on day 8 of cycle 1.
Lenalidomide (25 mg on days 1-21 of each cycle) and dexamethasone (40 mg/week) were the standard regimens for these drugs.
The primary endpoint was safety and tolerability. The secondary endpoint was overall response rate (ORR), duration of response, time to response, and infusion-related reactions (IRR).
The study also had an exploratory endpoint of progression-free survival (PFS).
Baseline characteristics
Patients were a median age of 59.5 years (range 34 – 74). About two thirds were younger than 65 and one third were between 65 and 75.
A little over half were male and most (86%) were white.
A little more than half (55%) had an ECOG score of 0, 41% were ECOG 1, and 5% were ECOG 2.
Patient disposition
As of the cutoff date of March 24, 8 of the 22 patients enrolled (36%) discontinued treatment: 1 due to an adverse event (AE), 1 due to progressive disease, and 6 patients (27%) proceeded to ASCT.
Dr Jakubowiak pointed out that response was censored at this point for patients who proceeded to transplant.
The median follow-up was 10.8 months (range, 4.0 – 12.5) and the median number of treatment cycles was 11.5 (range, 1.0 – 13.0).
“What is of interest to many of us,” Dr Jakubowiak said, “is that patients were escalated to the planned dose of 70 mg/m2 by cycle 2 except for 3 patients.”
Of the 3, 1 discontinued before day 1 of the second cycle due to toxicity, 1 had a dose reduction to 56 mg/m2 at day of the second cycle, and 1 escalated to 70 mg/m2 at day 8 of cycle 3.
Ultimately, all patients who remained on study were able to escalate to 70 mg/m2.
Safety
The hematologic treatment-emergent adverse events (TEAE) generally followed what has been observed in similar studies before, Dr Jakubowiak noted.
Hematologic TEAEs of all grades occurring in 30% or more of patients were lymphopenia (68%), thrombocytopenia (55%), anemia (46%), leukopenia (41%), and neutropenia (32%).
The most common non-hematologic TEAEs of all grades occurring in 30% of patients or more were diarrhea (73%), upper respiratory infection (59%) cough, constipation, and fatigue (50% each), dyspnea and insomnia (46%), nausea, rash, and back pain (41%), muscle spasm (36%), and vomiting, pain in extremity, hyperglycemia, and increased ALT (32%).
The most common grade 3/4 TEAEs were infrequent and many events had none of grade 3/4 severity.
The safety profile is consistent with what was previously reported for daratumumab or KRd, Dr Jakubowiak affirmed.
Serious TEAEs
Serious TEAEs occurred in 10 patients (46%), with many occurring in just 1 patient. Pulmonary embolism (PE) was the most frequent, occurring in 3 patients.
All patients were required to be on aspirin prophylaxis and 1 of the patients who had a PE discontinued therapy.
The number of patients with a serious TEAE reasonably related to an individual study drug were 3 (14%) for daratumumab, 5 (23%) for carfilzomib, 5 (23%) for lenalidomide, and 2 (9%) for dexamethasone.
The TEAEs of interest—tachycardia, congestive heart failure, and hypertension—occurred in a single patient each.
Overall, serious TEAEs were consistent with previous reports from KRd studies.
Echocardiogram assessment
Investigators conducted 30 systemic evaluations on the impact of this regimen on heart function. The investigators observed no change from baseline through the duration of treatment in patients’ left ventricular ejection fractions.
One patient developed congestive heart failure, possibly related to daratumumab or carfilzomib. This patient resumed treatment with a reduced carfilzomib dose, elected ASCT on study day 113, and ended treatment with a VGPR.
“In all,” Dr Jakubowiak said, “we feel that there is no apparent signal of adverse impact of the addition of daratumumab on cardiac function.”
Infusion times and reactions
Overall, IRRs occurred in 27% of the patients, “which appears lower than with previous daratumumab studies,” Dr Jakubowiak noted. And IRRs occurred more frequently during the first infusion than subsequent infusions.
The split-dose infusion time was very similar to that of second and subsequent cycles.
There were limited events related to infusions. All were grade 1 or 2 and most occurred in only a single patient.
Response rate
The median number of treatment cycles administered was 11.5 (range, 2.0 – 13.0). The best response was 100% PR or better, 91% achieved VGPR or better, 42% CR or better, and 29% a stringent CR.
The depth of response improved with duration of treatment. For example, the sCR rate increased from 5% after 4 cycles to 29% at the end of treatment.
PFS was an exploratory endpoint. One patient progressed at 10.8 months and the 12-month PFS rate was 94% with all patients alive.
Stem cell harvest and ASCT
“For many of us,” Dr Jakubowiak commented, “it’s also of interest how this regimen will impact stem cell harvest.”
Nineteen of 22 patients were deemed to be transplant eligible, and the median number of CD34+ cells collected from them was 10.4 x 106 cells/kg.
Patients had a median of 5 treatment cycles prior to stem cell harvest, and 14 (74%) had a VGPR or better prior to harvest.
The investigators believe stem cell yield was consistent with previous KRd studies.
Dr Jakubowiak commented that the deepening of response over time “is a phenomenon we think is important. . . . In all, the data from this small phase 1b study provide support for further evaluation of this regimen in newly diagnosed myeloma."
The study was funded by Janssen Research and Development, LLC.
*Data presented during the meeting differ from the abstract.
CHICAGO—Results of an open-label phase 1b study of daratumumab combined with carfilzomib, lenalidomide, and dexamethasone (KRd) in newly diagnosed multiple myeloma (MM) patients have shown the combination to be highly effective, with an overall response rate of 100%.
Ninety-one percent of patients achieved a very good partial response (VGPR) or better, and 43% achieved a complete response (CR) or better.
Investigators had hypothesized that rather than using autologous stem cell transplant (ASCT) to improve results of treatment with KRd, the combination could alternatively be improved by incorporating daratumumab into a KRd regimen.
Andrzej Jakubowiak, MD, of the University of Chicago Medical Center in Illinois, presented the findings of the MMY1001 study at the 2017 ASCO Annual Meeting (abstract 8000*).
“I think what was one of the more important developments in myeloma last year,” Dr Jakubowiak said, “was data from randomized studies showing that adding daratumumab to either lenalidomide and dexamethasone in the POLLUX study or bortezomib and dexamethasone, a proteasome inhibitor, in the CASTOR study, improves responses, depth of response, and . . . dramatically improved progression-free survival.”
“[W]e have now the rationale to potentially combine daratumumab with both an IMiD and proteasome inhibitor,” he explained, “which led to the development of this phase 1b study in which we combined daratumumab with KRd and evaluated tolerability and efficacy.”
Study design
Twenty-two transplant-eligible or -ineligible newly diagnosed MM patients were enrolled on the study.
Treatment duration was planned to be 13 cycles or less and patients had the option to move to transplant after 4 cycles.
They could have no clinically significant cardiac disease and echocardiogram was required prior to transplant.
The dosing schedule was the established dosing schema for daratumumab and KRd with 2 notable differences in the 28-day cycles.
First, the daratumumab dose was a split dose. So patients received 8 mg/kg on days 1-2 of cycle 1, 16 mg/kg a week on cycle 2, 16 mg/kg every 2 weeks on cycles 3 – 6, and every 4th week thereafter.
The second difference was carfilzomib dosing was a weekly regimen with escalation from 20 mg/m2 on day 1, cycle 1 to 70 mg/m2 on day 8 of cycle 1.
Lenalidomide (25 mg on days 1-21 of each cycle) and dexamethasone (40 mg/week) were the standard regimens for these drugs.
The primary endpoint was safety and tolerability. The secondary endpoint was overall response rate (ORR), duration of response, time to response, and infusion-related reactions (IRR).
The study also had an exploratory endpoint of progression-free survival (PFS).
Baseline characteristics
Patients were a median age of 59.5 years (range 34 – 74). About two thirds were younger than 65 and one third were between 65 and 75.
A little over half were male and most (86%) were white.
A little more than half (55%) had an ECOG score of 0, 41% were ECOG 1, and 5% were ECOG 2.
Patient disposition
As of the cutoff date of March 24, 8 of the 22 patients enrolled (36%) discontinued treatment: 1 due to an adverse event (AE), 1 due to progressive disease, and 6 patients (27%) proceeded to ASCT.
Dr Jakubowiak pointed out that response was censored at this point for patients who proceeded to transplant.
The median follow-up was 10.8 months (range, 4.0 – 12.5) and the median number of treatment cycles was 11.5 (range, 1.0 – 13.0).
“What is of interest to many of us,” Dr Jakubowiak said, “is that patients were escalated to the planned dose of 70 mg/m2 by cycle 2 except for 3 patients.”
Of the 3, 1 discontinued before day 1 of the second cycle due to toxicity, 1 had a dose reduction to 56 mg/m2 at day of the second cycle, and 1 escalated to 70 mg/m2 at day 8 of cycle 3.
Ultimately, all patients who remained on study were able to escalate to 70 mg/m2.
Safety
The hematologic treatment-emergent adverse events (TEAE) generally followed what has been observed in similar studies before, Dr Jakubowiak noted.
Hematologic TEAEs of all grades occurring in 30% or more of patients were lymphopenia (68%), thrombocytopenia (55%), anemia (46%), leukopenia (41%), and neutropenia (32%).
The most common non-hematologic TEAEs of all grades occurring in 30% of patients or more were diarrhea (73%), upper respiratory infection (59%) cough, constipation, and fatigue (50% each), dyspnea and insomnia (46%), nausea, rash, and back pain (41%), muscle spasm (36%), and vomiting, pain in extremity, hyperglycemia, and increased ALT (32%).
The most common grade 3/4 TEAEs were infrequent and many events had none of grade 3/4 severity.
The safety profile is consistent with what was previously reported for daratumumab or KRd, Dr Jakubowiak affirmed.
Serious TEAEs
Serious TEAEs occurred in 10 patients (46%), with many occurring in just 1 patient. Pulmonary embolism (PE) was the most frequent, occurring in 3 patients.
All patients were required to be on aspirin prophylaxis and 1 of the patients who had a PE discontinued therapy.
The number of patients with a serious TEAE reasonably related to an individual study drug were 3 (14%) for daratumumab, 5 (23%) for carfilzomib, 5 (23%) for lenalidomide, and 2 (9%) for dexamethasone.
The TEAEs of interest—tachycardia, congestive heart failure, and hypertension—occurred in a single patient each.
Overall, serious TEAEs were consistent with previous reports from KRd studies.
Echocardiogram assessment
Investigators conducted 30 systemic evaluations on the impact of this regimen on heart function. The investigators observed no change from baseline through the duration of treatment in patients’ left ventricular ejection fractions.
One patient developed congestive heart failure, possibly related to daratumumab or carfilzomib. This patient resumed treatment with a reduced carfilzomib dose, elected ASCT on study day 113, and ended treatment with a VGPR.
“In all,” Dr Jakubowiak said, “we feel that there is no apparent signal of adverse impact of the addition of daratumumab on cardiac function.”
Infusion times and reactions
Overall, IRRs occurred in 27% of the patients, “which appears lower than with previous daratumumab studies,” Dr Jakubowiak noted. And IRRs occurred more frequently during the first infusion than subsequent infusions.
The split-dose infusion time was very similar to that of second and subsequent cycles.
There were limited events related to infusions. All were grade 1 or 2 and most occurred in only a single patient.
Response rate
The median number of treatment cycles administered was 11.5 (range, 2.0 – 13.0). The best response was 100% PR or better, 91% achieved VGPR or better, 42% CR or better, and 29% a stringent CR.
The depth of response improved with duration of treatment. For example, the sCR rate increased from 5% after 4 cycles to 29% at the end of treatment.
PFS was an exploratory endpoint. One patient progressed at 10.8 months and the 12-month PFS rate was 94% with all patients alive.
Stem cell harvest and ASCT
“For many of us,” Dr Jakubowiak commented, “it’s also of interest how this regimen will impact stem cell harvest.”
Nineteen of 22 patients were deemed to be transplant eligible, and the median number of CD34+ cells collected from them was 10.4 x 106 cells/kg.
Patients had a median of 5 treatment cycles prior to stem cell harvest, and 14 (74%) had a VGPR or better prior to harvest.
The investigators believe stem cell yield was consistent with previous KRd studies.
Dr Jakubowiak commented that the deepening of response over time “is a phenomenon we think is important. . . . In all, the data from this small phase 1b study provide support for further evaluation of this regimen in newly diagnosed myeloma."
The study was funded by Janssen Research and Development, LLC.
*Data presented during the meeting differ from the abstract.
Differences emerge in new guidelines for managing FN in kids
A multidisciplinary, international panel of experts has updated earlier clinical practice guidelines on managing fever and neutropenia (FN) in children with cancer and in those undergoing hematopoietic stem cell transplantation (HSCT). And while most of the recommendations remained unchanged from the 2012 guidelines, a few key differences emerged. The changes included addition of a 4th generation cephalosporin for empirical antifungal therapy and refinements in risk stratification for invasive fungal disease (IFD), among others.
The new guidelines were published by The International Pediatric Fever and Neutropenia Guideline Panel in the Journal of Clinical Oncology.
The recommendations were organized into 3 major sections: initial presentation, ongoing management, and empirical antifungal therapy. The guidelines panel followed procedures previously validated for creating evidence-based guidelines and used the Appraisal of Guidelines for Research & Evaluation II instrument as a framework.
For the initial presentation of FN, the panel increased the quality of evidence from low to moderate in the recommendation to obtain peripheral blood cultures concurrent with central venous catheter cultures.
In the treatment of FN, the panel added a 4th-generation cephalosporin as empirical therapy in high-risk FN.
The panel refined the IFD risk factors and decreased the quality of evidence from moderate to low. Children with acute myeloid leukemia (AML), high-risk acute lymphoblastic leukemia (ALL), relapsed acute leukemia, those undergoing allogeneic HSCT, those with prolonged neutropenia, and those receiving high-dose corticosteroids are at high risk of IFD. All others should be categorized as IFD low risk.
The panel suggested serum galactomannan not be used to guide empirical antifungal management for prolonged FN lasting 96 hours or more in high-risk IFD patients. GM does not rule out non-Aspergillus molds, and therefore high negative values provide less useful predictions. Previously, the use of galactomannan was a weak recommendation.
The panel added a new recommendation against using fungal polymerase chain reaction (PCR) testing in blood. They explained PCR testing provides poor positive predictive values and negative predictive values are not sufficiently high to be clinically useful. Also, PCR testing is not yet standardized.
Another new recommendation is the addition of imaging of the abdomen in patients without localizing signs or symptoms. Even though the ideal imaging modality is not known, ultrasound is readily available, not associated with radiation exposure, and usually does not require sedation. For these reasons, the panel said it is preferable to computed tomography or magnetic resonance imaging.
The panel also changed a previously weak recommendation to administer empirical therapy for IFD low-risk patients with prolonged FN to a weak recommendation against administering therapy for these patients.
The panel's recommendations and their rationale can be found in the JCO article.
The guidelines update was supported by meeting grants from the Canadian Institutes of Health Research and the Garron Comprehensive Cancer Centre.
A multidisciplinary, international panel of experts has updated earlier clinical practice guidelines on managing fever and neutropenia (FN) in children with cancer and in those undergoing hematopoietic stem cell transplantation (HSCT). And while most of the recommendations remained unchanged from the 2012 guidelines, a few key differences emerged. The changes included addition of a 4th generation cephalosporin for empirical antifungal therapy and refinements in risk stratification for invasive fungal disease (IFD), among others.
The new guidelines were published by The International Pediatric Fever and Neutropenia Guideline Panel in the Journal of Clinical Oncology.
The recommendations were organized into 3 major sections: initial presentation, ongoing management, and empirical antifungal therapy. The guidelines panel followed procedures previously validated for creating evidence-based guidelines and used the Appraisal of Guidelines for Research & Evaluation II instrument as a framework.
For the initial presentation of FN, the panel increased the quality of evidence from low to moderate in the recommendation to obtain peripheral blood cultures concurrent with central venous catheter cultures.
In the treatment of FN, the panel added a 4th-generation cephalosporin as empirical therapy in high-risk FN.
The panel refined the IFD risk factors and decreased the quality of evidence from moderate to low. Children with acute myeloid leukemia (AML), high-risk acute lymphoblastic leukemia (ALL), relapsed acute leukemia, those undergoing allogeneic HSCT, those with prolonged neutropenia, and those receiving high-dose corticosteroids are at high risk of IFD. All others should be categorized as IFD low risk.
The panel suggested serum galactomannan not be used to guide empirical antifungal management for prolonged FN lasting 96 hours or more in high-risk IFD patients. GM does not rule out non-Aspergillus molds, and therefore high negative values provide less useful predictions. Previously, the use of galactomannan was a weak recommendation.
The panel added a new recommendation against using fungal polymerase chain reaction (PCR) testing in blood. They explained PCR testing provides poor positive predictive values and negative predictive values are not sufficiently high to be clinically useful. Also, PCR testing is not yet standardized.
Another new recommendation is the addition of imaging of the abdomen in patients without localizing signs or symptoms. Even though the ideal imaging modality is not known, ultrasound is readily available, not associated with radiation exposure, and usually does not require sedation. For these reasons, the panel said it is preferable to computed tomography or magnetic resonance imaging.
The panel also changed a previously weak recommendation to administer empirical therapy for IFD low-risk patients with prolonged FN to a weak recommendation against administering therapy for these patients.
The panel's recommendations and their rationale can be found in the JCO article.
The guidelines update was supported by meeting grants from the Canadian Institutes of Health Research and the Garron Comprehensive Cancer Centre.
A multidisciplinary, international panel of experts has updated earlier clinical practice guidelines on managing fever and neutropenia (FN) in children with cancer and in those undergoing hematopoietic stem cell transplantation (HSCT). And while most of the recommendations remained unchanged from the 2012 guidelines, a few key differences emerged. The changes included addition of a 4th generation cephalosporin for empirical antifungal therapy and refinements in risk stratification for invasive fungal disease (IFD), among others.
The new guidelines were published by The International Pediatric Fever and Neutropenia Guideline Panel in the Journal of Clinical Oncology.
The recommendations were organized into 3 major sections: initial presentation, ongoing management, and empirical antifungal therapy. The guidelines panel followed procedures previously validated for creating evidence-based guidelines and used the Appraisal of Guidelines for Research & Evaluation II instrument as a framework.
For the initial presentation of FN, the panel increased the quality of evidence from low to moderate in the recommendation to obtain peripheral blood cultures concurrent with central venous catheter cultures.
In the treatment of FN, the panel added a 4th-generation cephalosporin as empirical therapy in high-risk FN.
The panel refined the IFD risk factors and decreased the quality of evidence from moderate to low. Children with acute myeloid leukemia (AML), high-risk acute lymphoblastic leukemia (ALL), relapsed acute leukemia, those undergoing allogeneic HSCT, those with prolonged neutropenia, and those receiving high-dose corticosteroids are at high risk of IFD. All others should be categorized as IFD low risk.
The panel suggested serum galactomannan not be used to guide empirical antifungal management for prolonged FN lasting 96 hours or more in high-risk IFD patients. GM does not rule out non-Aspergillus molds, and therefore high negative values provide less useful predictions. Previously, the use of galactomannan was a weak recommendation.
The panel added a new recommendation against using fungal polymerase chain reaction (PCR) testing in blood. They explained PCR testing provides poor positive predictive values and negative predictive values are not sufficiently high to be clinically useful. Also, PCR testing is not yet standardized.
Another new recommendation is the addition of imaging of the abdomen in patients without localizing signs or symptoms. Even though the ideal imaging modality is not known, ultrasound is readily available, not associated with radiation exposure, and usually does not require sedation. For these reasons, the panel said it is preferable to computed tomography or magnetic resonance imaging.
The panel also changed a previously weak recommendation to administer empirical therapy for IFD low-risk patients with prolonged FN to a weak recommendation against administering therapy for these patients.
The panel's recommendations and their rationale can be found in the JCO article.
The guidelines update was supported by meeting grants from the Canadian Institutes of Health Research and the Garron Comprehensive Cancer Centre.
Group creates ‘authentic’ HSCs from endothelial cells
Researchers say they have found a way to convert adult mouse endothelial cells into “authentic” hematopoietic stem cells (HSCs).
The team says these HSCs have a transcriptome and long-term self-renewal capacity that are similar to those of adult HSCs that are produced naturally.
In addition, the lab-generated HSCs were capable of engraftment and multi-lineage reconstitution in mice.
“This is a game-changing breakthrough that brings us closer not only to treat blood disorders, but also to deciphering the complex biology of stem-cell self-renewal machinery,” said Shahin Rafii, MD, of Weill Cornell Medicine in New York, New York.
“This is exciting because it provides us with a path towards generating clinically useful quantities of normal stem cells for transplantation that may help us cure patients with genetic and acquired blood diseases,” added Joseph Scandura, MD, PhD, also of Weill Cornell Medicine.
Drs Scandura and Rafii and their colleagues described this research in Nature.
The researchers took vascular endothelial cells from adult mice and induced expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1.
The cells were grown and multiplied in co-culture with an engineered vascular niche.
This produced HSCs that were transplanted into irradiated mice.
The researchers said these HSCs were capable of long-term engraftment and hematopoietic reconstitution of myelopoiesis and both innate and adaptive immune function.
In addition, the HSCs were endowed with the same genetic attributes as normal adult HSCs.
If this method of generating HSCs in the lab can be scaled up and applied to humans, it could have wide-ranging clinical implications, according to the researchers.
“It might allow us to provide healthy stem cells to patients who need bone marrow donors but have no genetic match,” Dr Scandura said. “It could lead to new ways to cure leukemia and may help us correct genetic defects that cause blood diseases like sickle cell anemia.”
“More importantly, our vascular niche stem cell expansion model may be employed to clone the key unknown growth factors produced by this niche that are essential for self-perpetuation of stem cells,” Dr Rafii said. “Identification of those factors could be important for unraveling the secrets of stem cells’ longevity and translating the potential of stem cell therapy to the clinical setting.”
Researchers say they have found a way to convert adult mouse endothelial cells into “authentic” hematopoietic stem cells (HSCs).
The team says these HSCs have a transcriptome and long-term self-renewal capacity that are similar to those of adult HSCs that are produced naturally.
In addition, the lab-generated HSCs were capable of engraftment and multi-lineage reconstitution in mice.
“This is a game-changing breakthrough that brings us closer not only to treat blood disorders, but also to deciphering the complex biology of stem-cell self-renewal machinery,” said Shahin Rafii, MD, of Weill Cornell Medicine in New York, New York.
“This is exciting because it provides us with a path towards generating clinically useful quantities of normal stem cells for transplantation that may help us cure patients with genetic and acquired blood diseases,” added Joseph Scandura, MD, PhD, also of Weill Cornell Medicine.
Drs Scandura and Rafii and their colleagues described this research in Nature.
The researchers took vascular endothelial cells from adult mice and induced expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1.
The cells were grown and multiplied in co-culture with an engineered vascular niche.
This produced HSCs that were transplanted into irradiated mice.
The researchers said these HSCs were capable of long-term engraftment and hematopoietic reconstitution of myelopoiesis and both innate and adaptive immune function.
In addition, the HSCs were endowed with the same genetic attributes as normal adult HSCs.
If this method of generating HSCs in the lab can be scaled up and applied to humans, it could have wide-ranging clinical implications, according to the researchers.
“It might allow us to provide healthy stem cells to patients who need bone marrow donors but have no genetic match,” Dr Scandura said. “It could lead to new ways to cure leukemia and may help us correct genetic defects that cause blood diseases like sickle cell anemia.”
“More importantly, our vascular niche stem cell expansion model may be employed to clone the key unknown growth factors produced by this niche that are essential for self-perpetuation of stem cells,” Dr Rafii said. “Identification of those factors could be important for unraveling the secrets of stem cells’ longevity and translating the potential of stem cell therapy to the clinical setting.”
Researchers say they have found a way to convert adult mouse endothelial cells into “authentic” hematopoietic stem cells (HSCs).
The team says these HSCs have a transcriptome and long-term self-renewal capacity that are similar to those of adult HSCs that are produced naturally.
In addition, the lab-generated HSCs were capable of engraftment and multi-lineage reconstitution in mice.
“This is a game-changing breakthrough that brings us closer not only to treat blood disorders, but also to deciphering the complex biology of stem-cell self-renewal machinery,” said Shahin Rafii, MD, of Weill Cornell Medicine in New York, New York.
“This is exciting because it provides us with a path towards generating clinically useful quantities of normal stem cells for transplantation that may help us cure patients with genetic and acquired blood diseases,” added Joseph Scandura, MD, PhD, also of Weill Cornell Medicine.
Drs Scandura and Rafii and their colleagues described this research in Nature.
The researchers took vascular endothelial cells from adult mice and induced expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1.
The cells were grown and multiplied in co-culture with an engineered vascular niche.
This produced HSCs that were transplanted into irradiated mice.
The researchers said these HSCs were capable of long-term engraftment and hematopoietic reconstitution of myelopoiesis and both innate and adaptive immune function.
In addition, the HSCs were endowed with the same genetic attributes as normal adult HSCs.
If this method of generating HSCs in the lab can be scaled up and applied to humans, it could have wide-ranging clinical implications, according to the researchers.
“It might allow us to provide healthy stem cells to patients who need bone marrow donors but have no genetic match,” Dr Scandura said. “It could lead to new ways to cure leukemia and may help us correct genetic defects that cause blood diseases like sickle cell anemia.”
“More importantly, our vascular niche stem cell expansion model may be employed to clone the key unknown growth factors produced by this niche that are essential for self-perpetuation of stem cells,” Dr Rafii said. “Identification of those factors could be important for unraveling the secrets of stem cells’ longevity and translating the potential of stem cell therapy to the clinical setting.”
Intensive chemo upfront means DHL patients can skip HSCT
A new study suggests that patients with double-hit lymphoma (DHL) in first remission only benefit from an autologous hematopoietic stem cell transplant (auto-HSCT) if they received standard frontline chemotherapy.
Researchers looked at long-term outcomes for DHL patients who achieved remission and, overall, found that auto-HSCT did not significantly prolong remission or survival.
However, patients who received standard chemotherapy as frontline treatment did appear to benefit from auto-HSCT, as these patients had worse outcomes than patients who received intensive frontline chemotherapy.
This finding led the researchers to recommend that DHL patients receive intensive chemotherapy upfront and forgo subsequent auto-HSCT.
Daniel J. Landsburg, MD, of the University of Pennsylvania in Philadelphia, and his colleagues made these recommendations in the Journal of Clinical Oncology.
“A major dilemma for oncologists who treat [DHL] was whether or not to recommend the potentially harmful therapy of auto-[H]SCT to patients with this disease as a strategy to help keep them in remission,” Dr Landsburg said.
To gain some insight into the issue, Dr Landsburg and his colleagues looked at data on 159 patients from 19 academic medical centers across the US.
Patients were diagnosed with DHL between 2006 and 2015, and all achieved remission following frontline chemotherapy.
Thirty-five patients received standard frontline therapy—R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone).
The remaining patients received intensive frontline chemotherapy:
- 81 received DA-EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab)
- 32 received R-hyperCVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine)
- 11 received R-CODOX-M/IVAC (rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high-dose cytarabine).
Sixty-two patients underwent auto-HSCT, and 97 patients did not. There were no significant differences between these 2 patient groups at baseline.
“Our result is not explained by differences in patients’ overall health or disease features,” Dr Landsburg said. “The transplant and non-transplant arms of this study were very well-matched.”
Relapse and survival
For the entire patient cohort, the 3-year relapse-free survival (RFS) rate was 80%, and the 3-year overall survival (OS) rate was 87%.
There was no significant difference in RFS or OS between patients who underwent auto-HSCT and those who did not.
The RFS rate was 89% in patients who underwent auto-HSCT and 75% in patients who did not (P=0.12). The OS rate was 91% and 85%, respectively (P=0.74).
“Once these patients achieve remission, the data show they are likely to stay in remission,” Dr Landsburg said.
“In the absence of a large, randomized, controlled trial, which would be very challenging to carry out in this case, this is the best evidence we have, and it shows there’s no clear benefit to these patients undergoing auto-[H]SCT.”
Impact of frontline therapy
Patients who received R-CHOP upfront had worse RFS and OS than those who received intensive chemotherapy, although the OS difference was not significant.
RFS rates were 56% in patients who received R-CHOP, 88% in those who received DA-EPOCH-R, 87% in those who received R-hyperCVAD, and 91% in those who received R-CODOX-M/IVAC (P=0.003).
OS rates were 77% in patients who received R-CHOP, 87% in those who received DA-EPOCH-R, 90% in those who received R-hyperCVAD, and 100% in those who received R-CODOX-M/IVAC, respectively (P=0.36).
When the 3 intensive regimens were combined, the RFS rate was 88% (vs 56% for R-CHOP, P=0.002), and the OS rate was 90% (vs 77% for R-CHOP, P=0.13).
Frontline therapy and HSCT
Patients who received R-CHOP upfront benefited from auto-HSCT, but patients who received intensive chemotherapy did not.
The RFS was 51% for patients who received R-CHOP and did not undergo auto-HSCT, and it was 75% for patients who received R-CHOP followed by auto-HSCT.
The OS was 75% for patients who received R-CHOP and did not undergo auto-HSCT, and it was 83% for patients who received R-CHOP followed by auto-HSCT.
The RFS was 86% for patients who received intensive chemotherapy and did not undergo auto-HSCT, and it was 91% for patients who received intensive chemotherapy followed by auto-HSCT.
The OS was 89% for patients who received intensive chemotherapy and did not undergo auto-HSCT, and it was 92% for patients who received intensive chemotherapy followed by auto-HSCT.
An intergroup comparison showed a significant difference in RFS (P=0.003), which was driven by a significantly lower rate of RFS for patients who received R-CHOP without auto-HSCT, compared with patients who received intensive chemotherapy without auto-HSCT (P=0.003) or intensive chemotherapy with auto-HSCT (P=0.001).
“[I]f patients do go into remission with R-CHOP, it appears to be less durable, so, in these cases, going forward with auto-[H]SCT may still make sense,” Dr Landsburg said.
On the other hand, there was no significant difference between the groups with regard to OS (P=0.50).
Dr Landsburg said the next step for this research will be to study features of patients who don’t go into remission in order to understand why their disease is resistant to therapy and if that can be overcome with different treatment strategies. He also said it’s important to try to find more effective therapies for DHL patients who relapse.
A new study suggests that patients with double-hit lymphoma (DHL) in first remission only benefit from an autologous hematopoietic stem cell transplant (auto-HSCT) if they received standard frontline chemotherapy.
Researchers looked at long-term outcomes for DHL patients who achieved remission and, overall, found that auto-HSCT did not significantly prolong remission or survival.
However, patients who received standard chemotherapy as frontline treatment did appear to benefit from auto-HSCT, as these patients had worse outcomes than patients who received intensive frontline chemotherapy.
This finding led the researchers to recommend that DHL patients receive intensive chemotherapy upfront and forgo subsequent auto-HSCT.
Daniel J. Landsburg, MD, of the University of Pennsylvania in Philadelphia, and his colleagues made these recommendations in the Journal of Clinical Oncology.
“A major dilemma for oncologists who treat [DHL] was whether or not to recommend the potentially harmful therapy of auto-[H]SCT to patients with this disease as a strategy to help keep them in remission,” Dr Landsburg said.
To gain some insight into the issue, Dr Landsburg and his colleagues looked at data on 159 patients from 19 academic medical centers across the US.
Patients were diagnosed with DHL between 2006 and 2015, and all achieved remission following frontline chemotherapy.
Thirty-five patients received standard frontline therapy—R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone).
The remaining patients received intensive frontline chemotherapy:
- 81 received DA-EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab)
- 32 received R-hyperCVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine)
- 11 received R-CODOX-M/IVAC (rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high-dose cytarabine).
Sixty-two patients underwent auto-HSCT, and 97 patients did not. There were no significant differences between these 2 patient groups at baseline.
“Our result is not explained by differences in patients’ overall health or disease features,” Dr Landsburg said. “The transplant and non-transplant arms of this study were very well-matched.”
Relapse and survival
For the entire patient cohort, the 3-year relapse-free survival (RFS) rate was 80%, and the 3-year overall survival (OS) rate was 87%.
There was no significant difference in RFS or OS between patients who underwent auto-HSCT and those who did not.
The RFS rate was 89% in patients who underwent auto-HSCT and 75% in patients who did not (P=0.12). The OS rate was 91% and 85%, respectively (P=0.74).
“Once these patients achieve remission, the data show they are likely to stay in remission,” Dr Landsburg said.
“In the absence of a large, randomized, controlled trial, which would be very challenging to carry out in this case, this is the best evidence we have, and it shows there’s no clear benefit to these patients undergoing auto-[H]SCT.”
Impact of frontline therapy
Patients who received R-CHOP upfront had worse RFS and OS than those who received intensive chemotherapy, although the OS difference was not significant.
RFS rates were 56% in patients who received R-CHOP, 88% in those who received DA-EPOCH-R, 87% in those who received R-hyperCVAD, and 91% in those who received R-CODOX-M/IVAC (P=0.003).
OS rates were 77% in patients who received R-CHOP, 87% in those who received DA-EPOCH-R, 90% in those who received R-hyperCVAD, and 100% in those who received R-CODOX-M/IVAC, respectively (P=0.36).
When the 3 intensive regimens were combined, the RFS rate was 88% (vs 56% for R-CHOP, P=0.002), and the OS rate was 90% (vs 77% for R-CHOP, P=0.13).
Frontline therapy and HSCT
Patients who received R-CHOP upfront benefited from auto-HSCT, but patients who received intensive chemotherapy did not.
The RFS was 51% for patients who received R-CHOP and did not undergo auto-HSCT, and it was 75% for patients who received R-CHOP followed by auto-HSCT.
The OS was 75% for patients who received R-CHOP and did not undergo auto-HSCT, and it was 83% for patients who received R-CHOP followed by auto-HSCT.
The RFS was 86% for patients who received intensive chemotherapy and did not undergo auto-HSCT, and it was 91% for patients who received intensive chemotherapy followed by auto-HSCT.
The OS was 89% for patients who received intensive chemotherapy and did not undergo auto-HSCT, and it was 92% for patients who received intensive chemotherapy followed by auto-HSCT.
An intergroup comparison showed a significant difference in RFS (P=0.003), which was driven by a significantly lower rate of RFS for patients who received R-CHOP without auto-HSCT, compared with patients who received intensive chemotherapy without auto-HSCT (P=0.003) or intensive chemotherapy with auto-HSCT (P=0.001).
“[I]f patients do go into remission with R-CHOP, it appears to be less durable, so, in these cases, going forward with auto-[H]SCT may still make sense,” Dr Landsburg said.
On the other hand, there was no significant difference between the groups with regard to OS (P=0.50).
Dr Landsburg said the next step for this research will be to study features of patients who don’t go into remission in order to understand why their disease is resistant to therapy and if that can be overcome with different treatment strategies. He also said it’s important to try to find more effective therapies for DHL patients who relapse.
A new study suggests that patients with double-hit lymphoma (DHL) in first remission only benefit from an autologous hematopoietic stem cell transplant (auto-HSCT) if they received standard frontline chemotherapy.
Researchers looked at long-term outcomes for DHL patients who achieved remission and, overall, found that auto-HSCT did not significantly prolong remission or survival.
However, patients who received standard chemotherapy as frontline treatment did appear to benefit from auto-HSCT, as these patients had worse outcomes than patients who received intensive frontline chemotherapy.
This finding led the researchers to recommend that DHL patients receive intensive chemotherapy upfront and forgo subsequent auto-HSCT.
Daniel J. Landsburg, MD, of the University of Pennsylvania in Philadelphia, and his colleagues made these recommendations in the Journal of Clinical Oncology.
“A major dilemma for oncologists who treat [DHL] was whether or not to recommend the potentially harmful therapy of auto-[H]SCT to patients with this disease as a strategy to help keep them in remission,” Dr Landsburg said.
To gain some insight into the issue, Dr Landsburg and his colleagues looked at data on 159 patients from 19 academic medical centers across the US.
Patients were diagnosed with DHL between 2006 and 2015, and all achieved remission following frontline chemotherapy.
Thirty-five patients received standard frontline therapy—R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone).
The remaining patients received intensive frontline chemotherapy:
- 81 received DA-EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab)
- 32 received R-hyperCVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine)
- 11 received R-CODOX-M/IVAC (rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high-dose cytarabine).
Sixty-two patients underwent auto-HSCT, and 97 patients did not. There were no significant differences between these 2 patient groups at baseline.
“Our result is not explained by differences in patients’ overall health or disease features,” Dr Landsburg said. “The transplant and non-transplant arms of this study were very well-matched.”
Relapse and survival
For the entire patient cohort, the 3-year relapse-free survival (RFS) rate was 80%, and the 3-year overall survival (OS) rate was 87%.
There was no significant difference in RFS or OS between patients who underwent auto-HSCT and those who did not.
The RFS rate was 89% in patients who underwent auto-HSCT and 75% in patients who did not (P=0.12). The OS rate was 91% and 85%, respectively (P=0.74).
“Once these patients achieve remission, the data show they are likely to stay in remission,” Dr Landsburg said.
“In the absence of a large, randomized, controlled trial, which would be very challenging to carry out in this case, this is the best evidence we have, and it shows there’s no clear benefit to these patients undergoing auto-[H]SCT.”
Impact of frontline therapy
Patients who received R-CHOP upfront had worse RFS and OS than those who received intensive chemotherapy, although the OS difference was not significant.
RFS rates were 56% in patients who received R-CHOP, 88% in those who received DA-EPOCH-R, 87% in those who received R-hyperCVAD, and 91% in those who received R-CODOX-M/IVAC (P=0.003).
OS rates were 77% in patients who received R-CHOP, 87% in those who received DA-EPOCH-R, 90% in those who received R-hyperCVAD, and 100% in those who received R-CODOX-M/IVAC, respectively (P=0.36).
When the 3 intensive regimens were combined, the RFS rate was 88% (vs 56% for R-CHOP, P=0.002), and the OS rate was 90% (vs 77% for R-CHOP, P=0.13).
Frontline therapy and HSCT
Patients who received R-CHOP upfront benefited from auto-HSCT, but patients who received intensive chemotherapy did not.
The RFS was 51% for patients who received R-CHOP and did not undergo auto-HSCT, and it was 75% for patients who received R-CHOP followed by auto-HSCT.
The OS was 75% for patients who received R-CHOP and did not undergo auto-HSCT, and it was 83% for patients who received R-CHOP followed by auto-HSCT.
The RFS was 86% for patients who received intensive chemotherapy and did not undergo auto-HSCT, and it was 91% for patients who received intensive chemotherapy followed by auto-HSCT.
The OS was 89% for patients who received intensive chemotherapy and did not undergo auto-HSCT, and it was 92% for patients who received intensive chemotherapy followed by auto-HSCT.
An intergroup comparison showed a significant difference in RFS (P=0.003), which was driven by a significantly lower rate of RFS for patients who received R-CHOP without auto-HSCT, compared with patients who received intensive chemotherapy without auto-HSCT (P=0.003) or intensive chemotherapy with auto-HSCT (P=0.001).
“[I]f patients do go into remission with R-CHOP, it appears to be less durable, so, in these cases, going forward with auto-[H]SCT may still make sense,” Dr Landsburg said.
On the other hand, there was no significant difference between the groups with regard to OS (P=0.50).
Dr Landsburg said the next step for this research will be to study features of patients who don’t go into remission in order to understand why their disease is resistant to therapy and if that can be overcome with different treatment strategies. He also said it’s important to try to find more effective therapies for DHL patients who relapse.