CML

Key clinical point: Dasatinib and nilotinib as second-line treatments were equally effective, with a high molecular response (MR) and a tolerable safety profile in real-life patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: At 12 months, 47% and 38% of patients had a major MR and 18.2% and 16.6% had a deep MR in the dasatinib and nilotinib groups, respectively (P = .481). Grade 3-4 adverse events were more frequent in dasatinib vs. nilotinib groups (P = .003) with no effect on MR.

Study details: Findings are from a retrospective analysis of 131 patients with CML-CP who switched to second-line treatment with either dasatinib (n=72) or nilotinib (n=59) after frontline imatinib intolerance/resistance.

Disclosures: The authors did not declare any source of funding. M Breccia, M Martelli, and F Efficace reported receiving honoraria, personal fees, and grants from and being on the advisory board for various pharmaceutical companies. Other authors had no disclosures.

Source: Scalzulli E et al. Ann Hematol. 2021 Mar 7. doi: 10.1007/s00277-021-04477-0.

Key clinical point: Dasatinib and nilotinib as second-line treatments were equally effective, with a high molecular response (MR) and a tolerable safety profile in real-life patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: At 12 months, 47% and 38% of patients had a major MR and 18.2% and 16.6% had a deep MR in the dasatinib and nilotinib groups, respectively (P = .481). Grade 3-4 adverse events were more frequent in dasatinib vs. nilotinib groups (P = .003) with no effect on MR.

Study details: Findings are from a retrospective analysis of 131 patients with CML-CP who switched to second-line treatment with either dasatinib (n=72) or nilotinib (n=59) after frontline imatinib intolerance/resistance.

Disclosures: The authors did not declare any source of funding. M Breccia, M Martelli, and F Efficace reported receiving honoraria, personal fees, and grants from and being on the advisory board for various pharmaceutical companies. Other authors had no disclosures.

Source: Scalzulli E et al. Ann Hematol. 2021 Mar 7. doi: 10.1007/s00277-021-04477-0.

Key clinical point: Dasatinib and nilotinib as second-line treatments were equally effective, with a high molecular response (MR) and a tolerable safety profile in real-life patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: At 12 months, 47% and 38% of patients had a major MR and 18.2% and 16.6% had a deep MR in the dasatinib and nilotinib groups, respectively (P = .481). Grade 3-4 adverse events were more frequent in dasatinib vs. nilotinib groups (P = .003) with no effect on MR.

Study details: Findings are from a retrospective analysis of 131 patients with CML-CP who switched to second-line treatment with either dasatinib (n=72) or nilotinib (n=59) after frontline imatinib intolerance/resistance.

Disclosures: The authors did not declare any source of funding. M Breccia, M Martelli, and F Efficace reported receiving honoraria, personal fees, and grants from and being on the advisory board for various pharmaceutical companies. Other authors had no disclosures.

Source: Scalzulli E et al. Ann Hematol. 2021 Mar 7. doi: 10.1007/s00277-021-04477-0.

Key clinical point: More than 3 years of frontline nilotinib treatment was effective with sustained long-term high treatment-free remission (TFR) rates and manageable safety in patients with Philadelphia chromosome-positive (Ph+) chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Among patients who entered TFR, 41.6% remained in major molecular response (MMR), with 40.0% in MR^4.5, whereas 98.9% of patients who lost MMR regained after treatment reinitiation. No disease progression or CML-related deaths were observed, and the adverse event profile was consistent with that reported previously.

Study details: Findings are from a 5-year follow-up of phase 2 ENESTfreedom trial including 190 adult patients with Ph+ CML-CP who received at least 2 years of frontline nilotinib treatment, achieved MR^4.5, and attempted TFR after undergoing a 1-year nilotinib treatment consolidation phase.

Disclosures: This study was funded by Novartis Pharmaceuticals. The lead author along with other authors reported ties with various pharmaceutical companies including Novartis. P Aimone, S Li, and K Titorenko reported being employees of Novartis.

Source: Radich JP et al. Leukemia. 2021 Mar 11. doi: 10.1038/s41375-021-01205-5.

Key clinical point: More than 3 years of frontline nilotinib treatment was effective with sustained long-term high treatment-free remission (TFR) rates and manageable safety in patients with Philadelphia chromosome-positive (Ph+) chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Among patients who entered TFR, 41.6% remained in major molecular response (MMR), with 40.0% in MR^4.5, whereas 98.9% of patients who lost MMR regained after treatment reinitiation. No disease progression or CML-related deaths were observed, and the adverse event profile was consistent with that reported previously.

Study details: Findings are from a 5-year follow-up of phase 2 ENESTfreedom trial including 190 adult patients with Ph+ CML-CP who received at least 2 years of frontline nilotinib treatment, achieved MR^4.5, and attempted TFR after undergoing a 1-year nilotinib treatment consolidation phase.

Disclosures: This study was funded by Novartis Pharmaceuticals. The lead author along with other authors reported ties with various pharmaceutical companies including Novartis. P Aimone, S Li, and K Titorenko reported being employees of Novartis.

Source: Radich JP et al. Leukemia. 2021 Mar 11. doi: 10.1038/s41375-021-01205-5.

Key clinical point: More than 3 years of frontline nilotinib treatment was effective with sustained long-term high treatment-free remission (TFR) rates and manageable safety in patients with Philadelphia chromosome-positive (Ph+) chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Among patients who entered TFR, 41.6% remained in major molecular response (MMR), with 40.0% in MR^4.5, whereas 98.9% of patients who lost MMR regained after treatment reinitiation. No disease progression or CML-related deaths were observed, and the adverse event profile was consistent with that reported previously.

Study details: Findings are from a 5-year follow-up of phase 2 ENESTfreedom trial including 190 adult patients with Ph+ CML-CP who received at least 2 years of frontline nilotinib treatment, achieved MR^4.5, and attempted TFR after undergoing a 1-year nilotinib treatment consolidation phase.

Disclosures: This study was funded by Novartis Pharmaceuticals. The lead author along with other authors reported ties with various pharmaceutical companies including Novartis. P Aimone, S Li, and K Titorenko reported being employees of Novartis.

Source: Radich JP et al. Leukemia. 2021 Mar 11. doi: 10.1038/s41375-021-01205-5.

Key clinical point: Initial rate of BCR-ABL1 decline, measured as halving time, was a strong predictor of sustained treatment-free remission (TFR) post-tyrosine kinase inhibitor (TKI) cessation in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with firstline TKI therapies.

Major finding: Patients with a sustained TFR had a shorter BCR-ABL1 halving time vs. those with molecular relapse (10.1 vs. 21.7 days; P less than .001). The probability of sustained TFR was 80% vs. 4% among patients with halving time less than 9.35 days vs. more than 21.85 days (P less than .001).

Study details: Findings are from a retrospective analysis of 115 adult patients with CML-CP who attempted TFR and were followed up for at least 12 months post-TKI discontinuation.

Disclosures: The authors did not declare any source of funding. Some of the investigators including the lead author reported receiving honoraria and travel and accommodation expenses; being on the advisory board; and receiving research funding from various pharmaceutical companies.

Source: Shanmuganathan N et al. Blood. 2021 Mar 4. doi: 10.1182/blood.2020005514.

Key clinical point: Initial rate of BCR-ABL1 decline, measured as halving time, was a strong predictor of sustained treatment-free remission (TFR) post-tyrosine kinase inhibitor (TKI) cessation in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with firstline TKI therapies.

Major finding: Patients with a sustained TFR had a shorter BCR-ABL1 halving time vs. those with molecular relapse (10.1 vs. 21.7 days; P less than .001). The probability of sustained TFR was 80% vs. 4% among patients with halving time less than 9.35 days vs. more than 21.85 days (P less than .001).

Study details: Findings are from a retrospective analysis of 115 adult patients with CML-CP who attempted TFR and were followed up for at least 12 months post-TKI discontinuation.

Disclosures: The authors did not declare any source of funding. Some of the investigators including the lead author reported receiving honoraria and travel and accommodation expenses; being on the advisory board; and receiving research funding from various pharmaceutical companies.

Source: Shanmuganathan N et al. Blood. 2021 Mar 4. doi: 10.1182/blood.2020005514.

Key clinical point: Initial rate of BCR-ABL1 decline, measured as halving time, was a strong predictor of sustained treatment-free remission (TFR) post-tyrosine kinase inhibitor (TKI) cessation in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with firstline TKI therapies.

Major finding: Patients with a sustained TFR had a shorter BCR-ABL1 halving time vs. those with molecular relapse (10.1 vs. 21.7 days; P less than .001). The probability of sustained TFR was 80% vs. 4% among patients with halving time less than 9.35 days vs. more than 21.85 days (P less than .001).

Study details: Findings are from a retrospective analysis of 115 adult patients with CML-CP who attempted TFR and were followed up for at least 12 months post-TKI discontinuation.

Disclosures: The authors did not declare any source of funding. Some of the investigators including the lead author reported receiving honoraria and travel and accommodation expenses; being on the advisory board; and receiving research funding from various pharmaceutical companies.

Source: Shanmuganathan N et al. Blood. 2021 Mar 4. doi: 10.1182/blood.2020005514.

Key clinical point: High red blood cell distribution width (RDW) at diagnosis was associated with poor prognosis and treatment response in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with tyrosine kinase inhibitors (TKIs).

Major finding: High RDW was a significant predictor of poor overall survival (hazard ratio, [HR], 9.741; P = .005) and progression-free survival (HR, 16.74; P = .009). Patients with high RDW had worse treatment responses at 3 months (P = .03) and 6 months (P = .02).

Study details: Findings are from a retrospective analysis of 93 patients with newly diagnosed CML-CP and treated with TKIs. Patients were categorized into low (18.65% or lesser; n=58) and high (more than 18.65%; n=35) RDW groups.

Disclosures: No funding source was reported. The authors declared no conflicts of interest.

Source: Mao XL et al. Medicine. 2021 Mar 12. doi: 10.1097/MD.0000000000024003.

Key clinical point: High red blood cell distribution width (RDW) at diagnosis was associated with poor prognosis and treatment response in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with tyrosine kinase inhibitors (TKIs).

Major finding: High RDW was a significant predictor of poor overall survival (hazard ratio, [HR], 9.741; P = .005) and progression-free survival (HR, 16.74; P = .009). Patients with high RDW had worse treatment responses at 3 months (P = .03) and 6 months (P = .02).

Study details: Findings are from a retrospective analysis of 93 patients with newly diagnosed CML-CP and treated with TKIs. Patients were categorized into low (18.65% or lesser; n=58) and high (more than 18.65%; n=35) RDW groups.

Disclosures: No funding source was reported. The authors declared no conflicts of interest.

Source: Mao XL et al. Medicine. 2021 Mar 12. doi: 10.1097/MD.0000000000024003.

Key clinical point: High red blood cell distribution width (RDW) at diagnosis was associated with poor prognosis and treatment response in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with tyrosine kinase inhibitors (TKIs).

Major finding: High RDW was a significant predictor of poor overall survival (hazard ratio, [HR], 9.741; P = .005) and progression-free survival (HR, 16.74; P = .009). Patients with high RDW had worse treatment responses at 3 months (P = .03) and 6 months (P = .02).

Study details: Findings are from a retrospective analysis of 93 patients with newly diagnosed CML-CP and treated with TKIs. Patients were categorized into low (18.65% or lesser; n=58) and high (more than 18.65%; n=35) RDW groups.

Disclosures: No funding source was reported. The authors declared no conflicts of interest.

Source: Mao XL et al. Medicine. 2021 Mar 12. doi: 10.1097/MD.0000000000024003.

Among individuals who have received a hematopoietic stem cell transplant (HSCT), often used in the treatment of blood cancers, rates of survival are poor for those who develop COVID-19.

The probability of survival 30 days after being diagnosed with COVID-19 is only 68% for persons who have received an allogeneic HSCT and 67% for autologous HSCT recipients, according to new data from the Center for International Blood and Marrow Transplant Research.

These findings underscore the need for “stringent surveillance and aggressive treatment measures” in this population, Akshay Sharma, MBBS, of St. Jude Children’s Research Hospital, Memphis, and colleagues wrote.

The findings were published online March 1, 2021, in The Lancet Haematology.

The study is “of importance for physicians caring for HSCT recipients worldwide,” Mathieu Leclerc, MD, and Sébastien Maury, MD, Hôpital Henri Mondor, Créteil, France, commented in an accompanying editorial.
 

Study details

For their study, Dr. Sharma and colleagues analyzed outcomes for all HSCT recipients who developed COVID-19 and whose cases were reported to the CIBMTR. Of 318 such patients, 184 had undergone allogeneic HSCT, and 134 had undergone autologous HSCT.

Overall, about half of these patients (49%) had mild COVID-19.

Severe COVID-19 that required mechanical ventilation developed in 15% and 13% of the allogeneic and autologous HSCT recipients, respectively.

About one-fifth of patients died: 22% and 19% of allogeneic and autologous HSCT recipients, respectively.

Factors associated with greater mortality risk included age of 50 years or older (hazard ratio, 2.53), male sex (HR, 3.53), and development of COVID-19 within 12 months of undergoing HSCT (HR, 2.67).

Among autologous HSCT recipients, lymphoma was associated with higher mortality risk in comparison with a plasma cell disorder or myeloma (HR, 2.41), the authors noted.

“Two important messages can be drawn from the results reported by Sharma and colleagues,” Dr. Leclerc and Dr. Maury wrote in their editorial. “The first is the confirmation that the prognosis of COVID-19 is particularly poor in HSCT recipients, and that its prevention, in the absence of any specific curative treatment with sufficient efficacy, should be at the forefront of concerns.”

The second relates to the risk factors for death among HSCT recipients who develop COVID-19. In addition to previously known risk factors, such as age and gender, the investigators identified transplant-specific factors potentially associated with prognosis – namely, the nearly threefold increase in death among allogeneic HSCT recipients who develop COVID-19 within 12 months of transplant, they explained.

However, the findings are limited by a substantial amount of missing data, short follow-up, and the possibility of selection bias, they noted.

“Further large and well-designed studies with longer follow-up are needed to confirm and refine the results,” the editorialists wrote.

“[A] better understanding of the distinctive features of COVID-19 infection in HSCT recipients will be a necessary and essential step toward improvement of the remarkably poor prognosis observed in this setting,” they added.

The study was funded by the American Society of Hematology; the Leukemia and Lymphoma Society; the National Cancer Institute; the National Heart, Lung and Blood Institute; the National Institute of Allergy and Infectious Diseases; the National Institutes of Health; the Health Resources and Services Administration; and the Office of Naval Research. Dr. Sharma receives support for the conduct of industry-sponsored trials from Vertex Pharmaceuticals, CRISPR Therapeutics, and Novartis and consulting fees from Spotlight Therapeutics. Dr. Leclerc and Dr. Maury disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Among individuals who have received a hematopoietic stem cell transplant (HSCT), often used in the treatment of blood cancers, rates of survival are poor for those who develop COVID-19.

The probability of survival 30 days after being diagnosed with COVID-19 is only 68% for persons who have received an allogeneic HSCT and 67% for autologous HSCT recipients, according to new data from the Center for International Blood and Marrow Transplant Research.

These findings underscore the need for “stringent surveillance and aggressive treatment measures” in this population, Akshay Sharma, MBBS, of St. Jude Children’s Research Hospital, Memphis, and colleagues wrote.

The findings were published online March 1, 2021, in The Lancet Haematology.

The study is “of importance for physicians caring for HSCT recipients worldwide,” Mathieu Leclerc, MD, and Sébastien Maury, MD, Hôpital Henri Mondor, Créteil, France, commented in an accompanying editorial.
 

Study details

For their study, Dr. Sharma and colleagues analyzed outcomes for all HSCT recipients who developed COVID-19 and whose cases were reported to the CIBMTR. Of 318 such patients, 184 had undergone allogeneic HSCT, and 134 had undergone autologous HSCT.

Overall, about half of these patients (49%) had mild COVID-19.

Severe COVID-19 that required mechanical ventilation developed in 15% and 13% of the allogeneic and autologous HSCT recipients, respectively.

About one-fifth of patients died: 22% and 19% of allogeneic and autologous HSCT recipients, respectively.

Factors associated with greater mortality risk included age of 50 years or older (hazard ratio, 2.53), male sex (HR, 3.53), and development of COVID-19 within 12 months of undergoing HSCT (HR, 2.67).

Among autologous HSCT recipients, lymphoma was associated with higher mortality risk in comparison with a plasma cell disorder or myeloma (HR, 2.41), the authors noted.

“Two important messages can be drawn from the results reported by Sharma and colleagues,” Dr. Leclerc and Dr. Maury wrote in their editorial. “The first is the confirmation that the prognosis of COVID-19 is particularly poor in HSCT recipients, and that its prevention, in the absence of any specific curative treatment with sufficient efficacy, should be at the forefront of concerns.”

The second relates to the risk factors for death among HSCT recipients who develop COVID-19. In addition to previously known risk factors, such as age and gender, the investigators identified transplant-specific factors potentially associated with prognosis – namely, the nearly threefold increase in death among allogeneic HSCT recipients who develop COVID-19 within 12 months of transplant, they explained.

However, the findings are limited by a substantial amount of missing data, short follow-up, and the possibility of selection bias, they noted.

“Further large and well-designed studies with longer follow-up are needed to confirm and refine the results,” the editorialists wrote.

“[A] better understanding of the distinctive features of COVID-19 infection in HSCT recipients will be a necessary and essential step toward improvement of the remarkably poor prognosis observed in this setting,” they added.

The study was funded by the American Society of Hematology; the Leukemia and Lymphoma Society; the National Cancer Institute; the National Heart, Lung and Blood Institute; the National Institute of Allergy and Infectious Diseases; the National Institutes of Health; the Health Resources and Services Administration; and the Office of Naval Research. Dr. Sharma receives support for the conduct of industry-sponsored trials from Vertex Pharmaceuticals, CRISPR Therapeutics, and Novartis and consulting fees from Spotlight Therapeutics. Dr. Leclerc and Dr. Maury disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Among individuals who have received a hematopoietic stem cell transplant (HSCT), often used in the treatment of blood cancers, rates of survival are poor for those who develop COVID-19.

The probability of survival 30 days after being diagnosed with COVID-19 is only 68% for persons who have received an allogeneic HSCT and 67% for autologous HSCT recipients, according to new data from the Center for International Blood and Marrow Transplant Research.

These findings underscore the need for “stringent surveillance and aggressive treatment measures” in this population, Akshay Sharma, MBBS, of St. Jude Children’s Research Hospital, Memphis, and colleagues wrote.

The findings were published online March 1, 2021, in The Lancet Haematology.

The study is “of importance for physicians caring for HSCT recipients worldwide,” Mathieu Leclerc, MD, and Sébastien Maury, MD, Hôpital Henri Mondor, Créteil, France, commented in an accompanying editorial.
 

Study details

For their study, Dr. Sharma and colleagues analyzed outcomes for all HSCT recipients who developed COVID-19 and whose cases were reported to the CIBMTR. Of 318 such patients, 184 had undergone allogeneic HSCT, and 134 had undergone autologous HSCT.

Overall, about half of these patients (49%) had mild COVID-19.

Severe COVID-19 that required mechanical ventilation developed in 15% and 13% of the allogeneic and autologous HSCT recipients, respectively.

About one-fifth of patients died: 22% and 19% of allogeneic and autologous HSCT recipients, respectively.

Factors associated with greater mortality risk included age of 50 years or older (hazard ratio, 2.53), male sex (HR, 3.53), and development of COVID-19 within 12 months of undergoing HSCT (HR, 2.67).

Among autologous HSCT recipients, lymphoma was associated with higher mortality risk in comparison with a plasma cell disorder or myeloma (HR, 2.41), the authors noted.

“Two important messages can be drawn from the results reported by Sharma and colleagues,” Dr. Leclerc and Dr. Maury wrote in their editorial. “The first is the confirmation that the prognosis of COVID-19 is particularly poor in HSCT recipients, and that its prevention, in the absence of any specific curative treatment with sufficient efficacy, should be at the forefront of concerns.”

The second relates to the risk factors for death among HSCT recipients who develop COVID-19. In addition to previously known risk factors, such as age and gender, the investigators identified transplant-specific factors potentially associated with prognosis – namely, the nearly threefold increase in death among allogeneic HSCT recipients who develop COVID-19 within 12 months of transplant, they explained.

However, the findings are limited by a substantial amount of missing data, short follow-up, and the possibility of selection bias, they noted.

“Further large and well-designed studies with longer follow-up are needed to confirm and refine the results,” the editorialists wrote.

“[A] better understanding of the distinctive features of COVID-19 infection in HSCT recipients will be a necessary and essential step toward improvement of the remarkably poor prognosis observed in this setting,” they added.

The study was funded by the American Society of Hematology; the Leukemia and Lymphoma Society; the National Cancer Institute; the National Heart, Lung and Blood Institute; the National Institute of Allergy and Infectious Diseases; the National Institutes of Health; the Health Resources and Services Administration; and the Office of Naval Research. Dr. Sharma receives support for the conduct of industry-sponsored trials from Vertex Pharmaceuticals, CRISPR Therapeutics, and Novartis and consulting fees from Spotlight Therapeutics. Dr. Leclerc and Dr. Maury disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Omidubicel, an investigational enriched umbilical cord blood product being developed by Gamida Cell for transplantation in patients with blood cancers, appears to have some advantages over standard umbilical cord blood.

The results come from a global phase 3 trial (NCT02730299) presented at the annual meeting of the European Society for Blood and Bone Marrow Transplantation.

“Transplantation with omidubicel, compared to standard cord blood transplantation, results in faster hematopoietic recovery, fewer infections, and fewer days in hospital,” said coinvestigator Guillermo F. Sanz, MD, PhD, from the Hospital Universitari i Politècnic la Fe in Valencia, Spain.

“Omidubicel should be considered as the new standard of care for patients eligible for umbilical cord blood transplantation,” Dr. Sanz concluded.

Zachariah DeFilipp, MD, from Mass General Cancer Center in Boston, a hematopoietic stem cell transplantation specialist who was not involved in the study, said in an interview that “omidubicel significantly improves the engraftment after transplant, as compared to standard cord blood transplant. For patients that lack an HLA-matched donor, this approach can help overcome the prolonged cytopenias that occur with standard cord blood transplants in adults.”

Gamida Cell plans to submit these data for approval of omidubicel by the Food and Drug Administration in the fourth quarter of 2021.

Omidubicel is also being evaluated in a phase 1/2 clinical study in patients with severe aplastic anemia (NCT03173937).
 

Expanding possibilities

Although umbilical cord blood stem cell grafts come from a readily available source and show greater tolerance across HLA barriers than other sources (such as bone marrow), the relatively low dose of stem cells in each unit results in delayed hematopoietic recovery, increased transplant-related morbidity and mortality, and longer hospitalizations, Dr. Sanz said.

Omidubicel consists of two cryopreserved fractions from a single cord blood unit. The product contains both noncultured CD133-negative cells, including T cells, and CD133-positive cells that are then expanded ex vivo for 21 days in the presence of nicotinamide.

“Nicotinamide increases stem and progenitor cells, inhibits differentiation and increases migration, bone marrow homing, and engraftment efficiency while preserving cellular functionality and phenotype,” Dr. Sanz explained during his presentation.

In an earlier phase 1/2 trial in 36 patients with high-risk hematologic malignancies, omidubicel was associated with hematopoietic engraftment lasting at least 10 years.
 

Details of phase 3 trial results

The global phase 3 trial was conducted in 125 patients (aged 13-65 years) with high-risk malignancies, including acute myeloid and lymphoblastic leukemias, myelodysplastic syndrome, chronic myeloid leukemia, lymphomas, and rare leukemias. These patients were all eligible for allogeneic stem cell transplantation but did not have matched donors.

Patients were randomly assigned to receive hematopoietic reconstitution with either omidubicel (n = 52) or standard cord blood (n = 58).

At 42 days of follow-up, the median time to neutrophil engraftment in the intention-to-treat (ITT) population, the primary endpoint, was 12 days with omidubicel versus 22 days with standard cord blood (P < .001).

In the as-treated population – the 108 patients who actually received omidubicel or standard cord blood – median time to engraftment was 10.0 versus 20.5 days, respectively (P < .001).

Rates of neutrophil engraftment at 42 days were 96% with omidubicel versus 89% with standard cord blood.

The secondary endpoint of time-to-platelet engraftment in the ITT population also favored omidubicel, with a cumulative day 42 incidence rate of 55%, compared with 35% with standard cord blood (P = .028).

In the as-treated population, median times to platelet engraftment were 37 days and 50 days, respectively (P = .023). The cumulative rates of platelet engraftment at 100 days of follow-up were 83% and 73%, respectively.

The incidence of grade 2 or 3 bacterial or invasive fungal infections by day 100 in the ITT population was 37% among patients who received omidubicel, compared with 57% for patients who received standard cord blood (P = .027). Viral infections occurred in 10% versus 26% of patients, respectively.

The incidence of acute graft versus host disease at day 100 was similar between treatment groups, and there was no significant difference at 1 year.

Relapse and nonrelapse mortality rates, as well as disease-free and overall survival rates also did not differ between groups.

In the first 100 days post transplant, patients who received omidubicel were alive and out of the hospital for a median of 60.5 days, compared with 48 days for patients who received standard cord blood (P = .005).

The study was funded by Gamida Cell. Dr. Sanz reported receiving research funding from the company and several others, and consulting fees, honoraria, speakers bureau activity, and travel expenses from other companies. Dr. DeFilipp reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Omidubicel, an investigational enriched umbilical cord blood product being developed by Gamida Cell for transplantation in patients with blood cancers, appears to have some advantages over standard umbilical cord blood.

The results come from a global phase 3 trial (NCT02730299) presented at the annual meeting of the European Society for Blood and Bone Marrow Transplantation.

“Transplantation with omidubicel, compared to standard cord blood transplantation, results in faster hematopoietic recovery, fewer infections, and fewer days in hospital,” said coinvestigator Guillermo F. Sanz, MD, PhD, from the Hospital Universitari i Politècnic la Fe in Valencia, Spain.

“Omidubicel should be considered as the new standard of care for patients eligible for umbilical cord blood transplantation,” Dr. Sanz concluded.

Zachariah DeFilipp, MD, from Mass General Cancer Center in Boston, a hematopoietic stem cell transplantation specialist who was not involved in the study, said in an interview that “omidubicel significantly improves the engraftment after transplant, as compared to standard cord blood transplant. For patients that lack an HLA-matched donor, this approach can help overcome the prolonged cytopenias that occur with standard cord blood transplants in adults.”

Gamida Cell plans to submit these data for approval of omidubicel by the Food and Drug Administration in the fourth quarter of 2021.

Omidubicel is also being evaluated in a phase 1/2 clinical study in patients with severe aplastic anemia (NCT03173937).
 

Expanding possibilities

Although umbilical cord blood stem cell grafts come from a readily available source and show greater tolerance across HLA barriers than other sources (such as bone marrow), the relatively low dose of stem cells in each unit results in delayed hematopoietic recovery, increased transplant-related morbidity and mortality, and longer hospitalizations, Dr. Sanz said.

Omidubicel consists of two cryopreserved fractions from a single cord blood unit. The product contains both noncultured CD133-negative cells, including T cells, and CD133-positive cells that are then expanded ex vivo for 21 days in the presence of nicotinamide.

“Nicotinamide increases stem and progenitor cells, inhibits differentiation and increases migration, bone marrow homing, and engraftment efficiency while preserving cellular functionality and phenotype,” Dr. Sanz explained during his presentation.

In an earlier phase 1/2 trial in 36 patients with high-risk hematologic malignancies, omidubicel was associated with hematopoietic engraftment lasting at least 10 years.
 

Details of phase 3 trial results

The global phase 3 trial was conducted in 125 patients (aged 13-65 years) with high-risk malignancies, including acute myeloid and lymphoblastic leukemias, myelodysplastic syndrome, chronic myeloid leukemia, lymphomas, and rare leukemias. These patients were all eligible for allogeneic stem cell transplantation but did not have matched donors.

Patients were randomly assigned to receive hematopoietic reconstitution with either omidubicel (n = 52) or standard cord blood (n = 58).

At 42 days of follow-up, the median time to neutrophil engraftment in the intention-to-treat (ITT) population, the primary endpoint, was 12 days with omidubicel versus 22 days with standard cord blood (P < .001).

In the as-treated population – the 108 patients who actually received omidubicel or standard cord blood – median time to engraftment was 10.0 versus 20.5 days, respectively (P < .001).

Rates of neutrophil engraftment at 42 days were 96% with omidubicel versus 89% with standard cord blood.

The secondary endpoint of time-to-platelet engraftment in the ITT population also favored omidubicel, with a cumulative day 42 incidence rate of 55%, compared with 35% with standard cord blood (P = .028).

In the as-treated population, median times to platelet engraftment were 37 days and 50 days, respectively (P = .023). The cumulative rates of platelet engraftment at 100 days of follow-up were 83% and 73%, respectively.

The incidence of grade 2 or 3 bacterial or invasive fungal infections by day 100 in the ITT population was 37% among patients who received omidubicel, compared with 57% for patients who received standard cord blood (P = .027). Viral infections occurred in 10% versus 26% of patients, respectively.

The incidence of acute graft versus host disease at day 100 was similar between treatment groups, and there was no significant difference at 1 year.

Relapse and nonrelapse mortality rates, as well as disease-free and overall survival rates also did not differ between groups.

In the first 100 days post transplant, patients who received omidubicel were alive and out of the hospital for a median of 60.5 days, compared with 48 days for patients who received standard cord blood (P = .005).

The study was funded by Gamida Cell. Dr. Sanz reported receiving research funding from the company and several others, and consulting fees, honoraria, speakers bureau activity, and travel expenses from other companies. Dr. DeFilipp reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Omidubicel, an investigational enriched umbilical cord blood product being developed by Gamida Cell for transplantation in patients with blood cancers, appears to have some advantages over standard umbilical cord blood.

The results come from a global phase 3 trial (NCT02730299) presented at the annual meeting of the European Society for Blood and Bone Marrow Transplantation.

“Transplantation with omidubicel, compared to standard cord blood transplantation, results in faster hematopoietic recovery, fewer infections, and fewer days in hospital,” said coinvestigator Guillermo F. Sanz, MD, PhD, from the Hospital Universitari i Politècnic la Fe in Valencia, Spain.

“Omidubicel should be considered as the new standard of care for patients eligible for umbilical cord blood transplantation,” Dr. Sanz concluded.

Zachariah DeFilipp, MD, from Mass General Cancer Center in Boston, a hematopoietic stem cell transplantation specialist who was not involved in the study, said in an interview that “omidubicel significantly improves the engraftment after transplant, as compared to standard cord blood transplant. For patients that lack an HLA-matched donor, this approach can help overcome the prolonged cytopenias that occur with standard cord blood transplants in adults.”

Gamida Cell plans to submit these data for approval of omidubicel by the Food and Drug Administration in the fourth quarter of 2021.

Omidubicel is also being evaluated in a phase 1/2 clinical study in patients with severe aplastic anemia (NCT03173937).
 

Expanding possibilities

Although umbilical cord blood stem cell grafts come from a readily available source and show greater tolerance across HLA barriers than other sources (such as bone marrow), the relatively low dose of stem cells in each unit results in delayed hematopoietic recovery, increased transplant-related morbidity and mortality, and longer hospitalizations, Dr. Sanz said.

Omidubicel consists of two cryopreserved fractions from a single cord blood unit. The product contains both noncultured CD133-negative cells, including T cells, and CD133-positive cells that are then expanded ex vivo for 21 days in the presence of nicotinamide.

“Nicotinamide increases stem and progenitor cells, inhibits differentiation and increases migration, bone marrow homing, and engraftment efficiency while preserving cellular functionality and phenotype,” Dr. Sanz explained during his presentation.

In an earlier phase 1/2 trial in 36 patients with high-risk hematologic malignancies, omidubicel was associated with hematopoietic engraftment lasting at least 10 years.
 

Details of phase 3 trial results

The global phase 3 trial was conducted in 125 patients (aged 13-65 years) with high-risk malignancies, including acute myeloid and lymphoblastic leukemias, myelodysplastic syndrome, chronic myeloid leukemia, lymphomas, and rare leukemias. These patients were all eligible for allogeneic stem cell transplantation but did not have matched donors.

Patients were randomly assigned to receive hematopoietic reconstitution with either omidubicel (n = 52) or standard cord blood (n = 58).

At 42 days of follow-up, the median time to neutrophil engraftment in the intention-to-treat (ITT) population, the primary endpoint, was 12 days with omidubicel versus 22 days with standard cord blood (P < .001).

In the as-treated population – the 108 patients who actually received omidubicel or standard cord blood – median time to engraftment was 10.0 versus 20.5 days, respectively (P < .001).

Rates of neutrophil engraftment at 42 days were 96% with omidubicel versus 89% with standard cord blood.

The secondary endpoint of time-to-platelet engraftment in the ITT population also favored omidubicel, with a cumulative day 42 incidence rate of 55%, compared with 35% with standard cord blood (P = .028).

In the as-treated population, median times to platelet engraftment were 37 days and 50 days, respectively (P = .023). The cumulative rates of platelet engraftment at 100 days of follow-up were 83% and 73%, respectively.

The incidence of grade 2 or 3 bacterial or invasive fungal infections by day 100 in the ITT population was 37% among patients who received omidubicel, compared with 57% for patients who received standard cord blood (P = .027). Viral infections occurred in 10% versus 26% of patients, respectively.

The incidence of acute graft versus host disease at day 100 was similar between treatment groups, and there was no significant difference at 1 year.

Relapse and nonrelapse mortality rates, as well as disease-free and overall survival rates also did not differ between groups.

In the first 100 days post transplant, patients who received omidubicel were alive and out of the hospital for a median of 60.5 days, compared with 48 days for patients who received standard cord blood (P = .005).

The study was funded by Gamida Cell. Dr. Sanz reported receiving research funding from the company and several others, and consulting fees, honoraria, speakers bureau activity, and travel expenses from other companies. Dr. DeFilipp reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The first report on responses to COVID-19 vaccination among patients with cancer suggests that, for these patients, the immune response that occurs after the first dose of vaccine is reduced, in comparison with the response that occurs in healthy individuals.

The new findings, which are soon to be published as a preprint, cast doubt on the current U.K. policy of delaying the second dose of the vaccine.

Delaying the second dose can leave most patients with cancer wholly or partially unprotected, according to the researchers. Moreover, such a delay has implications for transmission of SARS-CoV-2 in the cancer patient’s environs as well as for the evolution of virus variants that could be of concern, the researchers concluded.

The data come from a British study that included 151 patients with cancer and 54 healthy control persons. All participants received the COVID-19 mRNA BNT162b2 vaccine (Pfizer-BioNTech).

This vaccine requires two doses. The first few participants in this study were given the second dose 21 days after they had received the first dose, but then national guidelines changed, and the remaining participants had to wait 12 weeks to receive their second dose.

The researchers reported that, among health controls, the immune efficacy of the first dose was very high (97% efficacious). By contrast, among patients with solid tumors, the immune efficacy of a single dose was strikingly low (39%), and it was even lower in patients with hematologic malignancies (13%).

The second dose of vaccine greatly and rapidly increased the immune efficacy in patients with solid tumors (95% within 2 weeks of receiving the second dose), the researchers added.

Too few patients with hematologic cancers had received the second dose before the study ended for clear conclusions to be drawn. Nevertheless, the available data suggest that 50% of patients with hematologic cancers who had received the booster at day 21 were seropositive at 5 weeks vs. only 8% of those who had not received the booster.

“Our data provide the first real-world evidence of immune efficacy following one dose of the Pfizer vaccine in immunocompromised patient populations [and] clearly show that the poor one-dose efficacy in cancer patients can be rescued with an early booster at day 21,” commented senior author Sheeba Irshad, MD, senior clinical lecturer, King’s College London.

“Based on our findings, we would recommend an urgent review of the vaccine strategy for clinically extremely vulnerable groups. Until then, it is important that cancer patients continue to observe all public health measures in place, such as social distancing and shielding when attending hospitals, even after vaccination,” Dr. Irshad added.

The paper, with first author Leticia Monin-Aldama, PhD, is scheduled to appear on the preprint server medRxiv. It has not undergone peer review. The paper was distributed to journalists, with comments from experts not involved in the study, by the UK Science Media Centre.

These data are “of immediate importance” to patients with cancer, commented Shoba Amarnath, PhD, Newcastle University research fellow, Laboratory of T-cell Regulation, Newcastle University Center for Cancer, Newcastle upon Tyne, England.

“These findings are consistent with our understanding. … We know that the immune system within cancer patients is compromised as compared to healthy controls,” Dr. Amarnath said. “The data in the study support the notion that, in solid cancer patients, a considerable delay in second dose will extend the period when cancer patients are at risk of SARS-CoV-2 infection.”

Although more data are required, “this study does raise the issue of whether patients with cancer, other diseases, or those undergoing therapies that affect the body’s immune response should be fast-tracked for their second vaccine dose,” commented Lawrence Young, PhD, professor of molecular oncology and director of the Warwick Cancer Research Center, University of Warwick, Coventry, England.

Stephen Evans, MSc, professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, underlined that the study is “essentially” observational and “inevitable limitations must be taken into account.

“Nevertheless, these results do suggest that the vaccines may well not protect those patients with cancer as well as those without cancer,” Mr. Evans said. He added that it is “important that this population continues to observe all COVID-19–associated measures, such as social distancing and shielding when attending hospitals, even after vaccination.”

Study details

Previous studies have shown that some patients with cancer have prolonged responses to SARS-CoV-2 infection, with ongoing immune dysregulation, inefficient seroconversion, and prolonged viral shedding.

There are few data, however, on how these patients respond to COVID-19 vaccination. The authors point out that, among the 18,860 individuals who received the Pfizer vaccine during its development trials, “none with an active oncological diagnosis was included.”

To investigate this issue, they launched the SARS-CoV-2 for Cancer Patients (SOAP-02) study.

The 151 patients with cancer who participated in this study were mostly elderly, the authors noted (75% were older than 65 years; the median age was 73 years). The majority (63%) had solid-tumor malignancies. Of those, 8% had late-stage disease and had been living with their cancer for more than 24 months.

The healthy control persons were vaccine-eligible primary health care workers who were not age matched to the cancer patients.

All participants received the first dose of vaccine; 31 (of 151) patients with cancer and 16 (of 54) healthy control persons received the second dose on day 21.

The remaining participants were scheduled to receive their second dose 12 weeks later (after the study ended), in line with the changes in the national guidelines.

The team reported that, approximately 21 days after receiving the first vaccine dose, the immune efficacy of the vaccine was estimated to be 97% among healthy control persons vs. 39% for patients with solid tumors and only 13% for those with hematologic malignancies (P < .0001 for both).

T-cell responses, as assessed via interferon-gamma and/or interleukin-2 production, were observed in 82% of healthy control persons, 71% of patients with solid tumors, and 50% of those with hematologic cancers.

Vaccine boosting at day 21 resulted in immune efficacy of 100% for healthy control persons and 95% for patients with solid tumors. In contrast, only 43% of those who did not receive the second dose were seropositive 2 weeks later.

Further analysis suggested that participants who did not have a serologic response were “spread evenly” across different cancer types, but the reduced responses were more frequent among patients who had received the vaccine within 15 days of cancer treatment, especially chemotherapy, and had undergone intensive treatments.

The SOAP study is sponsored by King’s College London and Guy’s and St. Thomas Trust Foundation NHS Trust. It is funded from grants from the KCL Charity, Cancer Research UK, and program grants from Breast Cancer Now. The investigators have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The first report on responses to COVID-19 vaccination among patients with cancer suggests that, for these patients, the immune response that occurs after the first dose of vaccine is reduced, in comparison with the response that occurs in healthy individuals.

The new findings, which are soon to be published as a preprint, cast doubt on the current U.K. policy of delaying the second dose of the vaccine.

Delaying the second dose can leave most patients with cancer wholly or partially unprotected, according to the researchers. Moreover, such a delay has implications for transmission of SARS-CoV-2 in the cancer patient’s environs as well as for the evolution of virus variants that could be of concern, the researchers concluded.

The data come from a British study that included 151 patients with cancer and 54 healthy control persons. All participants received the COVID-19 mRNA BNT162b2 vaccine (Pfizer-BioNTech).

This vaccine requires two doses. The first few participants in this study were given the second dose 21 days after they had received the first dose, but then national guidelines changed, and the remaining participants had to wait 12 weeks to receive their second dose.

The researchers reported that, among health controls, the immune efficacy of the first dose was very high (97% efficacious). By contrast, among patients with solid tumors, the immune efficacy of a single dose was strikingly low (39%), and it was even lower in patients with hematologic malignancies (13%).

The second dose of vaccine greatly and rapidly increased the immune efficacy in patients with solid tumors (95% within 2 weeks of receiving the second dose), the researchers added.

Too few patients with hematologic cancers had received the second dose before the study ended for clear conclusions to be drawn. Nevertheless, the available data suggest that 50% of patients with hematologic cancers who had received the booster at day 21 were seropositive at 5 weeks vs. only 8% of those who had not received the booster.

“Our data provide the first real-world evidence of immune efficacy following one dose of the Pfizer vaccine in immunocompromised patient populations [and] clearly show that the poor one-dose efficacy in cancer patients can be rescued with an early booster at day 21,” commented senior author Sheeba Irshad, MD, senior clinical lecturer, King’s College London.

“Based on our findings, we would recommend an urgent review of the vaccine strategy for clinically extremely vulnerable groups. Until then, it is important that cancer patients continue to observe all public health measures in place, such as social distancing and shielding when attending hospitals, even after vaccination,” Dr. Irshad added.

The paper, with first author Leticia Monin-Aldama, PhD, is scheduled to appear on the preprint server medRxiv. It has not undergone peer review. The paper was distributed to journalists, with comments from experts not involved in the study, by the UK Science Media Centre.

These data are “of immediate importance” to patients with cancer, commented Shoba Amarnath, PhD, Newcastle University research fellow, Laboratory of T-cell Regulation, Newcastle University Center for Cancer, Newcastle upon Tyne, England.

“These findings are consistent with our understanding. … We know that the immune system within cancer patients is compromised as compared to healthy controls,” Dr. Amarnath said. “The data in the study support the notion that, in solid cancer patients, a considerable delay in second dose will extend the period when cancer patients are at risk of SARS-CoV-2 infection.”

Although more data are required, “this study does raise the issue of whether patients with cancer, other diseases, or those undergoing therapies that affect the body’s immune response should be fast-tracked for their second vaccine dose,” commented Lawrence Young, PhD, professor of molecular oncology and director of the Warwick Cancer Research Center, University of Warwick, Coventry, England.

Stephen Evans, MSc, professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, underlined that the study is “essentially” observational and “inevitable limitations must be taken into account.

“Nevertheless, these results do suggest that the vaccines may well not protect those patients with cancer as well as those without cancer,” Mr. Evans said. He added that it is “important that this population continues to observe all COVID-19–associated measures, such as social distancing and shielding when attending hospitals, even after vaccination.”

Study details

Previous studies have shown that some patients with cancer have prolonged responses to SARS-CoV-2 infection, with ongoing immune dysregulation, inefficient seroconversion, and prolonged viral shedding.

There are few data, however, on how these patients respond to COVID-19 vaccination. The authors point out that, among the 18,860 individuals who received the Pfizer vaccine during its development trials, “none with an active oncological diagnosis was included.”

To investigate this issue, they launched the SARS-CoV-2 for Cancer Patients (SOAP-02) study.

The 151 patients with cancer who participated in this study were mostly elderly, the authors noted (75% were older than 65 years; the median age was 73 years). The majority (63%) had solid-tumor malignancies. Of those, 8% had late-stage disease and had been living with their cancer for more than 24 months.

The healthy control persons were vaccine-eligible primary health care workers who were not age matched to the cancer patients.

All participants received the first dose of vaccine; 31 (of 151) patients with cancer and 16 (of 54) healthy control persons received the second dose on day 21.

The remaining participants were scheduled to receive their second dose 12 weeks later (after the study ended), in line with the changes in the national guidelines.

The team reported that, approximately 21 days after receiving the first vaccine dose, the immune efficacy of the vaccine was estimated to be 97% among healthy control persons vs. 39% for patients with solid tumors and only 13% for those with hematologic malignancies (P < .0001 for both).

T-cell responses, as assessed via interferon-gamma and/or interleukin-2 production, were observed in 82% of healthy control persons, 71% of patients with solid tumors, and 50% of those with hematologic cancers.

Vaccine boosting at day 21 resulted in immune efficacy of 100% for healthy control persons and 95% for patients with solid tumors. In contrast, only 43% of those who did not receive the second dose were seropositive 2 weeks later.

Further analysis suggested that participants who did not have a serologic response were “spread evenly” across different cancer types, but the reduced responses were more frequent among patients who had received the vaccine within 15 days of cancer treatment, especially chemotherapy, and had undergone intensive treatments.

The SOAP study is sponsored by King’s College London and Guy’s and St. Thomas Trust Foundation NHS Trust. It is funded from grants from the KCL Charity, Cancer Research UK, and program grants from Breast Cancer Now. The investigators have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The first report on responses to COVID-19 vaccination among patients with cancer suggests that, for these patients, the immune response that occurs after the first dose of vaccine is reduced, in comparison with the response that occurs in healthy individuals.

The new findings, which are soon to be published as a preprint, cast doubt on the current U.K. policy of delaying the second dose of the vaccine.

Delaying the second dose can leave most patients with cancer wholly or partially unprotected, according to the researchers. Moreover, such a delay has implications for transmission of SARS-CoV-2 in the cancer patient’s environs as well as for the evolution of virus variants that could be of concern, the researchers concluded.

The data come from a British study that included 151 patients with cancer and 54 healthy control persons. All participants received the COVID-19 mRNA BNT162b2 vaccine (Pfizer-BioNTech).

This vaccine requires two doses. The first few participants in this study were given the second dose 21 days after they had received the first dose, but then national guidelines changed, and the remaining participants had to wait 12 weeks to receive their second dose.

The researchers reported that, among health controls, the immune efficacy of the first dose was very high (97% efficacious). By contrast, among patients with solid tumors, the immune efficacy of a single dose was strikingly low (39%), and it was even lower in patients with hematologic malignancies (13%).

The second dose of vaccine greatly and rapidly increased the immune efficacy in patients with solid tumors (95% within 2 weeks of receiving the second dose), the researchers added.

Too few patients with hematologic cancers had received the second dose before the study ended for clear conclusions to be drawn. Nevertheless, the available data suggest that 50% of patients with hematologic cancers who had received the booster at day 21 were seropositive at 5 weeks vs. only 8% of those who had not received the booster.

“Our data provide the first real-world evidence of immune efficacy following one dose of the Pfizer vaccine in immunocompromised patient populations [and] clearly show that the poor one-dose efficacy in cancer patients can be rescued with an early booster at day 21,” commented senior author Sheeba Irshad, MD, senior clinical lecturer, King’s College London.

“Based on our findings, we would recommend an urgent review of the vaccine strategy for clinically extremely vulnerable groups. Until then, it is important that cancer patients continue to observe all public health measures in place, such as social distancing and shielding when attending hospitals, even after vaccination,” Dr. Irshad added.

The paper, with first author Leticia Monin-Aldama, PhD, is scheduled to appear on the preprint server medRxiv. It has not undergone peer review. The paper was distributed to journalists, with comments from experts not involved in the study, by the UK Science Media Centre.

These data are “of immediate importance” to patients with cancer, commented Shoba Amarnath, PhD, Newcastle University research fellow, Laboratory of T-cell Regulation, Newcastle University Center for Cancer, Newcastle upon Tyne, England.

“These findings are consistent with our understanding. … We know that the immune system within cancer patients is compromised as compared to healthy controls,” Dr. Amarnath said. “The data in the study support the notion that, in solid cancer patients, a considerable delay in second dose will extend the period when cancer patients are at risk of SARS-CoV-2 infection.”

Although more data are required, “this study does raise the issue of whether patients with cancer, other diseases, or those undergoing therapies that affect the body’s immune response should be fast-tracked for their second vaccine dose,” commented Lawrence Young, PhD, professor of molecular oncology and director of the Warwick Cancer Research Center, University of Warwick, Coventry, England.

Stephen Evans, MSc, professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, underlined that the study is “essentially” observational and “inevitable limitations must be taken into account.

“Nevertheless, these results do suggest that the vaccines may well not protect those patients with cancer as well as those without cancer,” Mr. Evans said. He added that it is “important that this population continues to observe all COVID-19–associated measures, such as social distancing and shielding when attending hospitals, even after vaccination.”

Study details

Previous studies have shown that some patients with cancer have prolonged responses to SARS-CoV-2 infection, with ongoing immune dysregulation, inefficient seroconversion, and prolonged viral shedding.

There are few data, however, on how these patients respond to COVID-19 vaccination. The authors point out that, among the 18,860 individuals who received the Pfizer vaccine during its development trials, “none with an active oncological diagnosis was included.”

To investigate this issue, they launched the SARS-CoV-2 for Cancer Patients (SOAP-02) study.

The 151 patients with cancer who participated in this study were mostly elderly, the authors noted (75% were older than 65 years; the median age was 73 years). The majority (63%) had solid-tumor malignancies. Of those, 8% had late-stage disease and had been living with their cancer for more than 24 months.

The healthy control persons were vaccine-eligible primary health care workers who were not age matched to the cancer patients.

All participants received the first dose of vaccine; 31 (of 151) patients with cancer and 16 (of 54) healthy control persons received the second dose on day 21.

The remaining participants were scheduled to receive their second dose 12 weeks later (after the study ended), in line with the changes in the national guidelines.

The team reported that, approximately 21 days after receiving the first vaccine dose, the immune efficacy of the vaccine was estimated to be 97% among healthy control persons vs. 39% for patients with solid tumors and only 13% for those with hematologic malignancies (P < .0001 for both).

T-cell responses, as assessed via interferon-gamma and/or interleukin-2 production, were observed in 82% of healthy control persons, 71% of patients with solid tumors, and 50% of those with hematologic cancers.

Vaccine boosting at day 21 resulted in immune efficacy of 100% for healthy control persons and 95% for patients with solid tumors. In contrast, only 43% of those who did not receive the second dose were seropositive 2 weeks later.

Further analysis suggested that participants who did not have a serologic response were “spread evenly” across different cancer types, but the reduced responses were more frequent among patients who had received the vaccine within 15 days of cancer treatment, especially chemotherapy, and had undergone intensive treatments.

The SOAP study is sponsored by King’s College London and Guy’s and St. Thomas Trust Foundation NHS Trust. It is funded from grants from the KCL Charity, Cancer Research UK, and program grants from Breast Cancer Now. The investigators have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Although TFR is a reality on today's management of CML patients, it is important to emphasize a proper molecular monitoring after TKI discontinuation following the current NCCN and ELN guidelines. However, late relapses may occur after one year of therapy, although there are uncommon. In a recent letter to the editor in the journal Leukemia, investigators that participated in the EURO-SKI trial planned to follow patients beyond the 3 years scheduled in the trial and they reported the outcomes in what they called the AFTER-SKI trial. With a follow-up of 72 months, 12 out of 111 patients (10.8%) who were in TFR at 36 months, subsequently lost MMR. What is interesting is that the molecular status at 36 months appears highly predictive of later relapse, as only 1 patient out of 98 in MR4 at month 36 lost MMR in the following 3 years. Conversely, 11 of the 13 patients not in MR4 at month 36 lost MMR during follow-up.

For older CML patients not eligible for TFR or after TFR failure, long term therapy with TKI is the only option. However, we know that many patients can suffer from chronic AEs that will impact long term quality of life. A recent publication of the Italian phase III multicentric randomized OPTkIMA study aimed to evaluate if a progressive de‐escalation of TKIs was able to maintain the molecular response (MR^3.0) and improve Health Related Quality of Life (HRQoL). 166 elderly CML patients in stable MR^3.0/MR^4.0completed the first year of any TKI intermittent schedule, 1 month ON and 1 month OFF. The first-year probability of maintaining the MR^3.0 was 81%. No patients progressed to accelerated/blastic phase. All patients who lost the molecular response regained the MR^3.0 after resuming TKI continuously, and none suffered from TKI withdrawn syndrome. However, data related with quality of life was confounded by several factors and non-conclusive, for which longer follow up will be needed.
 

Although TFR is a reality on today's management of CML patients, it is important to emphasize a proper molecular monitoring after TKI discontinuation following the current NCCN and ELN guidelines. However, late relapses may occur after one year of therapy, although there are uncommon. In a recent letter to the editor in the journal Leukemia, investigators that participated in the EURO-SKI trial planned to follow patients beyond the 3 years scheduled in the trial and they reported the outcomes in what they called the AFTER-SKI trial. With a follow-up of 72 months, 12 out of 111 patients (10.8%) who were in TFR at 36 months, subsequently lost MMR. What is interesting is that the molecular status at 36 months appears highly predictive of later relapse, as only 1 patient out of 98 in MR4 at month 36 lost MMR in the following 3 years. Conversely, 11 of the 13 patients not in MR4 at month 36 lost MMR during follow-up.

For older CML patients not eligible for TFR or after TFR failure, long term therapy with TKI is the only option. However, we know that many patients can suffer from chronic AEs that will impact long term quality of life. A recent publication of the Italian phase III multicentric randomized OPTkIMA study aimed to evaluate if a progressive de‐escalation of TKIs was able to maintain the molecular response (MR^3.0) and improve Health Related Quality of Life (HRQoL). 166 elderly CML patients in stable MR^3.0/MR^4.0completed the first year of any TKI intermittent schedule, 1 month ON and 1 month OFF. The first-year probability of maintaining the MR^3.0 was 81%. No patients progressed to accelerated/blastic phase. All patients who lost the molecular response regained the MR^3.0 after resuming TKI continuously, and none suffered from TKI withdrawn syndrome. However, data related with quality of life was confounded by several factors and non-conclusive, for which longer follow up will be needed.
 

Although TFR is a reality on today's management of CML patients, it is important to emphasize a proper molecular monitoring after TKI discontinuation following the current NCCN and ELN guidelines. However, late relapses may occur after one year of therapy, although there are uncommon. In a recent letter to the editor in the journal Leukemia, investigators that participated in the EURO-SKI trial planned to follow patients beyond the 3 years scheduled in the trial and they reported the outcomes in what they called the AFTER-SKI trial. With a follow-up of 72 months, 12 out of 111 patients (10.8%) who were in TFR at 36 months, subsequently lost MMR. What is interesting is that the molecular status at 36 months appears highly predictive of later relapse, as only 1 patient out of 98 in MR4 at month 36 lost MMR in the following 3 years. Conversely, 11 of the 13 patients not in MR4 at month 36 lost MMR during follow-up.

For older CML patients not eligible for TFR or after TFR failure, long term therapy with TKI is the only option. However, we know that many patients can suffer from chronic AEs that will impact long term quality of life. A recent publication of the Italian phase III multicentric randomized OPTkIMA study aimed to evaluate if a progressive de‐escalation of TKIs was able to maintain the molecular response (MR^3.0) and improve Health Related Quality of Life (HRQoL). 166 elderly CML patients in stable MR^3.0/MR^4.0completed the first year of any TKI intermittent schedule, 1 month ON and 1 month OFF. The first-year probability of maintaining the MR^3.0 was 81%. No patients progressed to accelerated/blastic phase. All patients who lost the molecular response regained the MR^3.0 after resuming TKI continuously, and none suffered from TKI withdrawn syndrome. However, data related with quality of life was confounded by several factors and non-conclusive, for which longer follow up will be needed.
 

Key clinical point: G2677T/A and C3435T polymorphisms of multidrug resistance protein 1 (MDR1) play a role in response to imatinib mesylate (IM) in Caucasian population with chronic myeloid leukemia (CML).

Major finding: Variant T/A of G2677 marked responsiveness to IM therapy in Caucasian population under the recessive model (odds ratio [OR], 1.43; P = .01). The 3435TT genotype was significantly associated with increased resistance to IM therapy mainly in Caucasian population under dominant (OR, 1.49; P = .03) and heterozygous (OR, 1.52; P = .04) models.

Study details: Findings are from a meta-analysis of 17 studies involving 4,494 patients with CML; majority were in chronic phase.

Disclosures: The authors did not receive any financial support for research, authorship, and/or publication of this article. The authors declared no potential conflicts of interest.

Source: Louati N et al. J Oncol Pharm Pract. 2021 Feb 10. doi: 10.1177/1078155220981150.

Key clinical point: G2677T/A and C3435T polymorphisms of multidrug resistance protein 1 (MDR1) play a role in response to imatinib mesylate (IM) in Caucasian population with chronic myeloid leukemia (CML).

Major finding: Variant T/A of G2677 marked responsiveness to IM therapy in Caucasian population under the recessive model (odds ratio [OR], 1.43; P = .01). The 3435TT genotype was significantly associated with increased resistance to IM therapy mainly in Caucasian population under dominant (OR, 1.49; P = .03) and heterozygous (OR, 1.52; P = .04) models.

Study details: Findings are from a meta-analysis of 17 studies involving 4,494 patients with CML; majority were in chronic phase.

Disclosures: The authors did not receive any financial support for research, authorship, and/or publication of this article. The authors declared no potential conflicts of interest.

Source: Louati N et al. J Oncol Pharm Pract. 2021 Feb 10. doi: 10.1177/1078155220981150.

Key clinical point: G2677T/A and C3435T polymorphisms of multidrug resistance protein 1 (MDR1) play a role in response to imatinib mesylate (IM) in Caucasian population with chronic myeloid leukemia (CML).

Major finding: Variant T/A of G2677 marked responsiveness to IM therapy in Caucasian population under the recessive model (odds ratio [OR], 1.43; P = .01). The 3435TT genotype was significantly associated with increased resistance to IM therapy mainly in Caucasian population under dominant (OR, 1.49; P = .03) and heterozygous (OR, 1.52; P = .04) models.

Study details: Findings are from a meta-analysis of 17 studies involving 4,494 patients with CML; majority were in chronic phase.

Disclosures: The authors did not receive any financial support for research, authorship, and/or publication of this article. The authors declared no potential conflicts of interest.

Source: Louati N et al. J Oncol Pharm Pract. 2021 Feb 10. doi: 10.1177/1078155220981150.

Key clinical point: De-escalation of tyrosine kinase inhibitor (TKI) therapy from continuous to intermittent (1 month ON/OFF) schedule effectively maintained molecular response 3/4 (MR3/4) during the first year in elderly patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: The 1-year probability of maintaining MR3 with intermittent TKI therapy was 81% (95% confidence interval, 75%-87%). Of the 39 patients who lost MR, 95% regained at least MR3 within 6 months of resuming continuous TKI. No treatment-related adverse events were reported.

Study details: Findings are from the first interim analysis of the phase 3 OPTkIMA trial including 185 patients with CML-CP (age, 60 years or more) who were in stable MR3/4 after 2 or more years of daily treatment with TKI.

Disclosures: The authors did not report any source of funding. The lead author had no disclosures. Some other coinvestigators reported ties with various pharmaceutical companies.

Source: Malagola M et al. Cancer Med. 2021 Feb 16. doi: 10.1002/cam4.3778.

Key clinical point: De-escalation of tyrosine kinase inhibitor (TKI) therapy from continuous to intermittent (1 month ON/OFF) schedule effectively maintained molecular response 3/4 (MR3/4) during the first year in elderly patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: The 1-year probability of maintaining MR3 with intermittent TKI therapy was 81% (95% confidence interval, 75%-87%). Of the 39 patients who lost MR, 95% regained at least MR3 within 6 months of resuming continuous TKI. No treatment-related adverse events were reported.

Study details: Findings are from the first interim analysis of the phase 3 OPTkIMA trial including 185 patients with CML-CP (age, 60 years or more) who were in stable MR3/4 after 2 or more years of daily treatment with TKI.

Disclosures: The authors did not report any source of funding. The lead author had no disclosures. Some other coinvestigators reported ties with various pharmaceutical companies.

Source: Malagola M et al. Cancer Med. 2021 Feb 16. doi: 10.1002/cam4.3778.

Key clinical point: De-escalation of tyrosine kinase inhibitor (TKI) therapy from continuous to intermittent (1 month ON/OFF) schedule effectively maintained molecular response 3/4 (MR3/4) during the first year in elderly patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: The 1-year probability of maintaining MR3 with intermittent TKI therapy was 81% (95% confidence interval, 75%-87%). Of the 39 patients who lost MR, 95% regained at least MR3 within 6 months of resuming continuous TKI. No treatment-related adverse events were reported.

Study details: Findings are from the first interim analysis of the phase 3 OPTkIMA trial including 185 patients with CML-CP (age, 60 years or more) who were in stable MR3/4 after 2 or more years of daily treatment with TKI.

Disclosures: The authors did not report any source of funding. The lead author had no disclosures. Some other coinvestigators reported ties with various pharmaceutical companies.

Source: Malagola M et al. Cancer Med. 2021 Feb 16. doi: 10.1002/cam4.3778.