CML

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.

Key clinical point: BCR/ABL transcript type B3a2_e14a2 is more common than B2a2_e13a2 in patients with chronic myeloid leukemia (CML) with B3a2_e14a2 being more common in women than men.

Major finding: The overall estimated prevalence was highest for B3a2_e14a2 transcript (54%), followed by B2a2_e13a2 (39%) and dual B2a2_e13a2/B3a2_e14a2 (1.11%) transcripts (all P less than .0001), with B3a2_e14a2 being more prevalent in women vs. men (60.6% vs. 51.1%; P less than .0001).

Study details: Findings are from a meta-analysis of 34 studies that evaluated the prevalence of main BCR/ABL transcript types in patients with CML.

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

Source: Ghalesardi OK et al. Leuk Res. 2021 Jan 19. doi: 10.1016/j.leukres.2021.106512.

Key clinical point: BCR/ABL transcript type B3a2_e14a2 is more common than B2a2_e13a2 in patients with chronic myeloid leukemia (CML) with B3a2_e14a2 being more common in women than men.

Major finding: The overall estimated prevalence was highest for B3a2_e14a2 transcript (54%), followed by B2a2_e13a2 (39%) and dual B2a2_e13a2/B3a2_e14a2 (1.11%) transcripts (all P less than .0001), with B3a2_e14a2 being more prevalent in women vs. men (60.6% vs. 51.1%; P less than .0001).

Study details: Findings are from a meta-analysis of 34 studies that evaluated the prevalence of main BCR/ABL transcript types in patients with CML.

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

Source: Ghalesardi OK et al. Leuk Res. 2021 Jan 19. doi: 10.1016/j.leukres.2021.106512.

Key clinical point: BCR/ABL transcript type B3a2_e14a2 is more common than B2a2_e13a2 in patients with chronic myeloid leukemia (CML) with B3a2_e14a2 being more common in women than men.

Major finding: The overall estimated prevalence was highest for B3a2_e14a2 transcript (54%), followed by B2a2_e13a2 (39%) and dual B2a2_e13a2/B3a2_e14a2 (1.11%) transcripts (all P less than .0001), with B3a2_e14a2 being more prevalent in women vs. men (60.6% vs. 51.1%; P less than .0001).

Study details: Findings are from a meta-analysis of 34 studies that evaluated the prevalence of main BCR/ABL transcript types in patients with CML.

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

Source: Ghalesardi OK et al. Leuk Res. 2021 Jan 19. doi: 10.1016/j.leukres.2021.106512.

Key clinical point: Right ventricular systolic pressure (RVSP) increased significantly following dasatinib therapy in some patients with chronic-phase chronic myeloid leukemia (CML-CP), leading to dasatinib-induced pulmonary arterial hypertension (D-PAH) and consequent therapy discontinuation.

Major finding: During a median of 36.2 months of dasatinib therapy, mean RSVP increased significantly and gradually (P less than .001). Overall, 56 patients had RVSP over 40 mmHg, of which 51.8% of patients were diagnosed with D-PAH with clinical symptoms, all ultimately switching to other tyrosine kinase inhibitors.

Study details: Findings are from an analysis of a cohort of 451 patients with CML-CP who underwent 2D-echocardiography at least once at baseline and/or during dasatinib therapy (mean dose, 85 mg/day) as frontline (n=196) and subsequent line (n=255).

Disclosures: This study was funded by Korea Leukemia Bank. The authors declared no conflicts of interest.

Source: Lee SE et al. Cancer Med. 2021 Feb 15. doi: 10.1002/cam4.3588.

Key clinical point: Right ventricular systolic pressure (RVSP) increased significantly following dasatinib therapy in some patients with chronic-phase chronic myeloid leukemia (CML-CP), leading to dasatinib-induced pulmonary arterial hypertension (D-PAH) and consequent therapy discontinuation.

Major finding: During a median of 36.2 months of dasatinib therapy, mean RSVP increased significantly and gradually (P less than .001). Overall, 56 patients had RVSP over 40 mmHg, of which 51.8% of patients were diagnosed with D-PAH with clinical symptoms, all ultimately switching to other tyrosine kinase inhibitors.

Study details: Findings are from an analysis of a cohort of 451 patients with CML-CP who underwent 2D-echocardiography at least once at baseline and/or during dasatinib therapy (mean dose, 85 mg/day) as frontline (n=196) and subsequent line (n=255).

Disclosures: This study was funded by Korea Leukemia Bank. The authors declared no conflicts of interest.

Source: Lee SE et al. Cancer Med. 2021 Feb 15. doi: 10.1002/cam4.3588.

Key clinical point: Right ventricular systolic pressure (RVSP) increased significantly following dasatinib therapy in some patients with chronic-phase chronic myeloid leukemia (CML-CP), leading to dasatinib-induced pulmonary arterial hypertension (D-PAH) and consequent therapy discontinuation.

Major finding: During a median of 36.2 months of dasatinib therapy, mean RSVP increased significantly and gradually (P less than .001). Overall, 56 patients had RVSP over 40 mmHg, of which 51.8% of patients were diagnosed with D-PAH with clinical symptoms, all ultimately switching to other tyrosine kinase inhibitors.

Study details: Findings are from an analysis of a cohort of 451 patients with CML-CP who underwent 2D-echocardiography at least once at baseline and/or during dasatinib therapy (mean dose, 85 mg/day) as frontline (n=196) and subsequent line (n=255).

Disclosures: This study was funded by Korea Leukemia Bank. The authors declared no conflicts of interest.

Source: Lee SE et al. Cancer Med. 2021 Feb 15. doi: 10.1002/cam4.3588.

Key clinical point: Asciminib is a safe and effective drug in patients with chronic myeloid leukemia (CML) without treatment alternatives in common clinical practice.

Major finding: After a median of 8.8 months on asciminib, the cumulative response rates of complete hematologic response, complete cytogenetic response, and major molecular response were 100%, 66%, and 41%, respectively. Improvement in baseline response and maintenance of baseline response were observed in 55% and 90% of patients, respectively. At last evaluation, 87% of patients remained on asciminib treatment with none discontinuing because of treatment-emergent adverse events.

Study details: Findings are from a retrospective analysis of 31 BCR-ABL1-positive patients with CML treated with asciminib. Patients were heavily treated and switched to asciminib because of intolerance (n=22) or resistance (n=9) to prior tyrosine kinase inhibitors. All patients were treated under the managed-access program by Novartis.

Disclosures: No information on funding was available. Four of the authors including the lead author reported being on advisory committees, receiving funds, and/or speaker honoraria from various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Garcia-Gutiérrez V et al. Blood Cancer J. 2021 Feb 9. doi: 10.1038/s41408-021-00420-8.

Key clinical point: Asciminib is a safe and effective drug in patients with chronic myeloid leukemia (CML) without treatment alternatives in common clinical practice.

Major finding: After a median of 8.8 months on asciminib, the cumulative response rates of complete hematologic response, complete cytogenetic response, and major molecular response were 100%, 66%, and 41%, respectively. Improvement in baseline response and maintenance of baseline response were observed in 55% and 90% of patients, respectively. At last evaluation, 87% of patients remained on asciminib treatment with none discontinuing because of treatment-emergent adverse events.

Study details: Findings are from a retrospective analysis of 31 BCR-ABL1-positive patients with CML treated with asciminib. Patients were heavily treated and switched to asciminib because of intolerance (n=22) or resistance (n=9) to prior tyrosine kinase inhibitors. All patients were treated under the managed-access program by Novartis.

Disclosures: No information on funding was available. Four of the authors including the lead author reported being on advisory committees, receiving funds, and/or speaker honoraria from various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Garcia-Gutiérrez V et al. Blood Cancer J. 2021 Feb 9. doi: 10.1038/s41408-021-00420-8.

Key clinical point: Asciminib is a safe and effective drug in patients with chronic myeloid leukemia (CML) without treatment alternatives in common clinical practice.

Major finding: After a median of 8.8 months on asciminib, the cumulative response rates of complete hematologic response, complete cytogenetic response, and major molecular response were 100%, 66%, and 41%, respectively. Improvement in baseline response and maintenance of baseline response were observed in 55% and 90% of patients, respectively. At last evaluation, 87% of patients remained on asciminib treatment with none discontinuing because of treatment-emergent adverse events.

Study details: Findings are from a retrospective analysis of 31 BCR-ABL1-positive patients with CML treated with asciminib. Patients were heavily treated and switched to asciminib because of intolerance (n=22) or resistance (n=9) to prior tyrosine kinase inhibitors. All patients were treated under the managed-access program by Novartis.

Disclosures: No information on funding was available. Four of the authors including the lead author reported being on advisory committees, receiving funds, and/or speaker honoraria from various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Garcia-Gutiérrez V et al. Blood Cancer J. 2021 Feb 9. doi: 10.1038/s41408-021-00420-8.

Key clinical point: At 2 years, molecular recurrence-free survival (MRFS) after imatinib discontinuation was observed in over half of the patients with chronic phase-chronic myeloid leukemia (CML-CP) with sustained molecular response of 4log (MR4). MR of 4.5log (MR4.5) was associated with a lower risk of relapse.

Major finding: At 24 months, MRFS was 54% (95% CI, 39%-75%). Molecular relapse was observed in 42% of patients. All patients reachieved major molecular response after resuming imatinib. MR4.5 at discontinuation was associated with a lower risk of molecular relapse (odds ratio, 0.32; P = .03).

Study details: Findings are from a prospective study that evaluated treatment-free survival after imatinib discontinuation in 31 patients with CML-CP with sustained MR4 for at least 12 months and treated with first-line imatinib for at least 36 months.

Disclosures: No specific funding was received for this study. The authors declared no conflicts of interest.

Source: Seguro FS et al. Leuk Res. 2021 Jan 21. doi: 10.1016/j.leukres.2021.106516.

Key clinical point: At 2 years, molecular recurrence-free survival (MRFS) after imatinib discontinuation was observed in over half of the patients with chronic phase-chronic myeloid leukemia (CML-CP) with sustained molecular response of 4log (MR4). MR of 4.5log (MR4.5) was associated with a lower risk of relapse.

Major finding: At 24 months, MRFS was 54% (95% CI, 39%-75%). Molecular relapse was observed in 42% of patients. All patients reachieved major molecular response after resuming imatinib. MR4.5 at discontinuation was associated with a lower risk of molecular relapse (odds ratio, 0.32; P = .03).

Study details: Findings are from a prospective study that evaluated treatment-free survival after imatinib discontinuation in 31 patients with CML-CP with sustained MR4 for at least 12 months and treated with first-line imatinib for at least 36 months.

Disclosures: No specific funding was received for this study. The authors declared no conflicts of interest.

Source: Seguro FS et al. Leuk Res. 2021 Jan 21. doi: 10.1016/j.leukres.2021.106516.

Key clinical point: At 2 years, molecular recurrence-free survival (MRFS) after imatinib discontinuation was observed in over half of the patients with chronic phase-chronic myeloid leukemia (CML-CP) with sustained molecular response of 4log (MR4). MR of 4.5log (MR4.5) was associated with a lower risk of relapse.

Major finding: At 24 months, MRFS was 54% (95% CI, 39%-75%). Molecular relapse was observed in 42% of patients. All patients reachieved major molecular response after resuming imatinib. MR4.5 at discontinuation was associated with a lower risk of molecular relapse (odds ratio, 0.32; P = .03).

Study details: Findings are from a prospective study that evaluated treatment-free survival after imatinib discontinuation in 31 patients with CML-CP with sustained MR4 for at least 12 months and treated with first-line imatinib for at least 36 months.

Disclosures: No specific funding was received for this study. The authors declared no conflicts of interest.

Source: Seguro FS et al. Leuk Res. 2021 Jan 21. doi: 10.1016/j.leukres.2021.106516.

Key clinical point: Asian patients with chronic myeloid leukemia in chronic phase (CML-CP) with a higher dasatinib dose adjusted for body weight (dose/BW) experienced a higher risk of dose-limiting toxicities (DLTs). The fixed starting dose of dasatinib 100 mg may not be optimal in Asian patients.

Major finding: By 36 months after initiation of dasatinib 100 mg once daily (OD) as frontline therapy, 55.9% of patients experienced at least 1 DLT. Higher dasatinib dose/BW was associated with a higher risk of DLT occurrence (odds ratio, 4.84; P = .03).

Study details: This study assessed the effect of a fixed starting dose of dasatinib (100 mg OD) in 102 Asian patients with newly diagnosed CML-CP.

Disclosures: This study was funded by the National Research Foundation of Korea, the Foundation of Pharmacy Education and Research, and the Research Institutes of Pharmaceutical Sciences (Seoul National University). The lead author had no disclosures. DW Kim reported the use of clinical data collected from a separate research study (funded by Bristol-Myers Squibb) for this study.

Source: Shin H et al. Clin Lymphoma Myeloma Leuk. 2021 Feb 1 doi: 10.1016/j.clml.2021.01.020.

Key clinical point: Asian patients with chronic myeloid leukemia in chronic phase (CML-CP) with a higher dasatinib dose adjusted for body weight (dose/BW) experienced a higher risk of dose-limiting toxicities (DLTs). The fixed starting dose of dasatinib 100 mg may not be optimal in Asian patients.

Major finding: By 36 months after initiation of dasatinib 100 mg once daily (OD) as frontline therapy, 55.9% of patients experienced at least 1 DLT. Higher dasatinib dose/BW was associated with a higher risk of DLT occurrence (odds ratio, 4.84; P = .03).

Study details: This study assessed the effect of a fixed starting dose of dasatinib (100 mg OD) in 102 Asian patients with newly diagnosed CML-CP.

Disclosures: This study was funded by the National Research Foundation of Korea, the Foundation of Pharmacy Education and Research, and the Research Institutes of Pharmaceutical Sciences (Seoul National University). The lead author had no disclosures. DW Kim reported the use of clinical data collected from a separate research study (funded by Bristol-Myers Squibb) for this study.

Source: Shin H et al. Clin Lymphoma Myeloma Leuk. 2021 Feb 1 doi: 10.1016/j.clml.2021.01.020.

Key clinical point: Asian patients with chronic myeloid leukemia in chronic phase (CML-CP) with a higher dasatinib dose adjusted for body weight (dose/BW) experienced a higher risk of dose-limiting toxicities (DLTs). The fixed starting dose of dasatinib 100 mg may not be optimal in Asian patients.

Major finding: By 36 months after initiation of dasatinib 100 mg once daily (OD) as frontline therapy, 55.9% of patients experienced at least 1 DLT. Higher dasatinib dose/BW was associated with a higher risk of DLT occurrence (odds ratio, 4.84; P = .03).

Study details: This study assessed the effect of a fixed starting dose of dasatinib (100 mg OD) in 102 Asian patients with newly diagnosed CML-CP.

Disclosures: This study was funded by the National Research Foundation of Korea, the Foundation of Pharmacy Education and Research, and the Research Institutes of Pharmaceutical Sciences (Seoul National University). The lead author had no disclosures. DW Kim reported the use of clinical data collected from a separate research study (funded by Bristol-Myers Squibb) for this study.

Source: Shin H et al. Clin Lymphoma Myeloma Leuk. 2021 Feb 1 doi: 10.1016/j.clml.2021.01.020.

Key clinical point: Late relapses do occur after tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic-phase chronic myeloid leukemia (CML-CP) in treatment-free remission (TFR) at 36 months, with molecular response (MR) status at 36 months being highly predictive of subsequent molecular relapse.

Major finding: During a follow-up of 72 months, 10.8% of patients in TFR at 36 months lost major MR. Not being in MR4 at 36 months of TKI discontinuation was associated with an 85% higher risk of molecular relapse during the subsequent 3 years.

Study details: Findings are from the 6-year follow-up (AFTER-SKI) of 111 patients with CML-CP who were in TFR at 36 months after TKI discontinuation from the EURO-SKI trial.

Disclosures: This study was funded by Lund University and Skane University Hospital. U Olsson-Strömberg, P Koskenvesa, and D Žáčková reported consulting for, being on speaker’s and advisory boards, or receiving honoraria from various pharmaceutical companies. The remaining authors had no disclosures.

Source: Richter J et al. Leukemia. 2021 Feb 15. doi: 10.1038/s41375-021-01173-w.

Key clinical point: Late relapses do occur after tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic-phase chronic myeloid leukemia (CML-CP) in treatment-free remission (TFR) at 36 months, with molecular response (MR) status at 36 months being highly predictive of subsequent molecular relapse.

Major finding: During a follow-up of 72 months, 10.8% of patients in TFR at 36 months lost major MR. Not being in MR4 at 36 months of TKI discontinuation was associated with an 85% higher risk of molecular relapse during the subsequent 3 years.

Study details: Findings are from the 6-year follow-up (AFTER-SKI) of 111 patients with CML-CP who were in TFR at 36 months after TKI discontinuation from the EURO-SKI trial.

Disclosures: This study was funded by Lund University and Skane University Hospital. U Olsson-Strömberg, P Koskenvesa, and D Žáčková reported consulting for, being on speaker’s and advisory boards, or receiving honoraria from various pharmaceutical companies. The remaining authors had no disclosures.

Source: Richter J et al. Leukemia. 2021 Feb 15. doi: 10.1038/s41375-021-01173-w.

Key clinical point: Late relapses do occur after tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic-phase chronic myeloid leukemia (CML-CP) in treatment-free remission (TFR) at 36 months, with molecular response (MR) status at 36 months being highly predictive of subsequent molecular relapse.

Major finding: During a follow-up of 72 months, 10.8% of patients in TFR at 36 months lost major MR. Not being in MR4 at 36 months of TKI discontinuation was associated with an 85% higher risk of molecular relapse during the subsequent 3 years.

Study details: Findings are from the 6-year follow-up (AFTER-SKI) of 111 patients with CML-CP who were in TFR at 36 months after TKI discontinuation from the EURO-SKI trial.

Disclosures: This study was funded by Lund University and Skane University Hospital. U Olsson-Strömberg, P Koskenvesa, and D Žáčková reported consulting for, being on speaker’s and advisory boards, or receiving honoraria from various pharmaceutical companies. The remaining authors had no disclosures.

Source: Richter J et al. Leukemia. 2021 Feb 15. doi: 10.1038/s41375-021-01173-w.