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Myeloma: Can Lymphopenia Help Predict Patient Outcomes?
TOPLINE:
The analysis of 11,427 US Deparment of Veterans Affairs (VA) hospital patients with multiple myeloma (MM) reveals that lymphopenia affects 53% of patients at diagnosis. The median overall survival was 2.7 years in patients with severely low absolute lymphocyte count vs 4.2 years in those with normal counts.
METHODOLOGY:
- Researchers evaluated 11,427 patients diagnosed with MM between 2000 and 2019 at VA medical centers using absolute lymphocyte count obtained closest to diagnosis and up to 2.5 years thereafter.
- Patients were stratified into three absolute lymphocyte count categories: Severely low (less than 1 × 10⁹/μL), low (1 × 10⁹/μL to 1.5 × 10⁹/μL), and normal (> 1.5 × 10⁹/μL).
- Analysis excluded patients with acute and chronic leukemias, aplastic anemia, myelodysplastic syndrome, hairy cell leukemia, or myeloproliferative neoplasms before MM diagnosis.
- Follow-up duration extended from diagnosis until development of another hematologic malignancy, death, truncation date (15 years after diagnosis), or study end date.
TAKEAWAY:
- Lymphopenia was present in 53% of patients at MM diagnosis and was associated with inferior overall survival.
- Median overall survival for patients with severely low, low, and normal absolute lymphocyte count at diagnosis was 2.7 years, 3.3 years, and 4.2 years, respectively (P < .001).
- Persistent or new development of lymphopenia during treatment and follow-up was linked to inferior overall survival.
- Standard induction therapy with lenalidomide, bortezomib, and dexamethasone did not overcome inferior outcomes in patients with lymphopenia, showing median overall survival of 3.6 years, 4.6 years, and 5.7 years among patients with severely low, low, and normal baseline absolute lymphocyte count, respectively (P less than .001).
IN PRACTICE:
“Because immune dysregulation and immunosenescence in the bone marrow microenvironment are reflected in the peripheral blood lymphocyte count and peripheral blood markers may, in turn, correlate with clinical features and outcome in MM, we sought to identify clinical features correlating with peripheral blood lymphopenia and evaluate absolute lymphocyte count at diagnosis as a predictor of outcome in MM and in the context of standard induction treatment,” the authors wrote.
SOURCE:
This study was led by Grace M. Ferri and Cenk Yildirim, Boston Medical Center in Boston. It was published online in Blood Advances.
LIMITATIONS:
This study population consisted predominantly of male participants due to being conducted in the VA system. Additionally, researchers acknowledged that lymphopenia could not be exclusively attributed to MM, as other treatments common in older populations might contribute. The use of alkylating agents like cyclophosphamide and melphalan during treatment could also influence lymphopenia levels.
DISCLOSURES:
Individual-level data underlying this study are available to researchers with VA regulatory approval, consistent with VA policy.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
The analysis of 11,427 US Deparment of Veterans Affairs (VA) hospital patients with multiple myeloma (MM) reveals that lymphopenia affects 53% of patients at diagnosis. The median overall survival was 2.7 years in patients with severely low absolute lymphocyte count vs 4.2 years in those with normal counts.
METHODOLOGY:
- Researchers evaluated 11,427 patients diagnosed with MM between 2000 and 2019 at VA medical centers using absolute lymphocyte count obtained closest to diagnosis and up to 2.5 years thereafter.
- Patients were stratified into three absolute lymphocyte count categories: Severely low (less than 1 × 10⁹/μL), low (1 × 10⁹/μL to 1.5 × 10⁹/μL), and normal (> 1.5 × 10⁹/μL).
- Analysis excluded patients with acute and chronic leukemias, aplastic anemia, myelodysplastic syndrome, hairy cell leukemia, or myeloproliferative neoplasms before MM diagnosis.
- Follow-up duration extended from diagnosis until development of another hematologic malignancy, death, truncation date (15 years after diagnosis), or study end date.
TAKEAWAY:
- Lymphopenia was present in 53% of patients at MM diagnosis and was associated with inferior overall survival.
- Median overall survival for patients with severely low, low, and normal absolute lymphocyte count at diagnosis was 2.7 years, 3.3 years, and 4.2 years, respectively (P < .001).
- Persistent or new development of lymphopenia during treatment and follow-up was linked to inferior overall survival.
- Standard induction therapy with lenalidomide, bortezomib, and dexamethasone did not overcome inferior outcomes in patients with lymphopenia, showing median overall survival of 3.6 years, 4.6 years, and 5.7 years among patients with severely low, low, and normal baseline absolute lymphocyte count, respectively (P less than .001).
IN PRACTICE:
“Because immune dysregulation and immunosenescence in the bone marrow microenvironment are reflected in the peripheral blood lymphocyte count and peripheral blood markers may, in turn, correlate with clinical features and outcome in MM, we sought to identify clinical features correlating with peripheral blood lymphopenia and evaluate absolute lymphocyte count at diagnosis as a predictor of outcome in MM and in the context of standard induction treatment,” the authors wrote.
SOURCE:
This study was led by Grace M. Ferri and Cenk Yildirim, Boston Medical Center in Boston. It was published online in Blood Advances.
LIMITATIONS:
This study population consisted predominantly of male participants due to being conducted in the VA system. Additionally, researchers acknowledged that lymphopenia could not be exclusively attributed to MM, as other treatments common in older populations might contribute. The use of alkylating agents like cyclophosphamide and melphalan during treatment could also influence lymphopenia levels.
DISCLOSURES:
Individual-level data underlying this study are available to researchers with VA regulatory approval, consistent with VA policy.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
The analysis of 11,427 US Deparment of Veterans Affairs (VA) hospital patients with multiple myeloma (MM) reveals that lymphopenia affects 53% of patients at diagnosis. The median overall survival was 2.7 years in patients with severely low absolute lymphocyte count vs 4.2 years in those with normal counts.
METHODOLOGY:
- Researchers evaluated 11,427 patients diagnosed with MM between 2000 and 2019 at VA medical centers using absolute lymphocyte count obtained closest to diagnosis and up to 2.5 years thereafter.
- Patients were stratified into three absolute lymphocyte count categories: Severely low (less than 1 × 10⁹/μL), low (1 × 10⁹/μL to 1.5 × 10⁹/μL), and normal (> 1.5 × 10⁹/μL).
- Analysis excluded patients with acute and chronic leukemias, aplastic anemia, myelodysplastic syndrome, hairy cell leukemia, or myeloproliferative neoplasms before MM diagnosis.
- Follow-up duration extended from diagnosis until development of another hematologic malignancy, death, truncation date (15 years after diagnosis), or study end date.
TAKEAWAY:
- Lymphopenia was present in 53% of patients at MM diagnosis and was associated with inferior overall survival.
- Median overall survival for patients with severely low, low, and normal absolute lymphocyte count at diagnosis was 2.7 years, 3.3 years, and 4.2 years, respectively (P < .001).
- Persistent or new development of lymphopenia during treatment and follow-up was linked to inferior overall survival.
- Standard induction therapy with lenalidomide, bortezomib, and dexamethasone did not overcome inferior outcomes in patients with lymphopenia, showing median overall survival of 3.6 years, 4.6 years, and 5.7 years among patients with severely low, low, and normal baseline absolute lymphocyte count, respectively (P less than .001).
IN PRACTICE:
“Because immune dysregulation and immunosenescence in the bone marrow microenvironment are reflected in the peripheral blood lymphocyte count and peripheral blood markers may, in turn, correlate with clinical features and outcome in MM, we sought to identify clinical features correlating with peripheral blood lymphopenia and evaluate absolute lymphocyte count at diagnosis as a predictor of outcome in MM and in the context of standard induction treatment,” the authors wrote.
SOURCE:
This study was led by Grace M. Ferri and Cenk Yildirim, Boston Medical Center in Boston. It was published online in Blood Advances.
LIMITATIONS:
This study population consisted predominantly of male participants due to being conducted in the VA system. Additionally, researchers acknowledged that lymphopenia could not be exclusively attributed to MM, as other treatments common in older populations might contribute. The use of alkylating agents like cyclophosphamide and melphalan during treatment could also influence lymphopenia levels.
DISCLOSURES:
Individual-level data underlying this study are available to researchers with VA regulatory approval, consistent with VA policy.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
To Combat Leukemia, Researchers Harness CD37
TOPLINE:
METHODOLOGY:
- Researchers analyzed CD37 expression in 55 untreated, newly diagnosed primary AML samples, along with normal hematopoietic stem cells, peripheral blood mononuclear cells, and AML cell lines.
- Analysis included internalization assays using anti-CD37 antibody conjugated to fluorochrome Alexa Fluor 647, with cells incubated for 2 hours at 37 °C vs on ice to quantify surface and intracellular CD37.
- Investigators conducted in vivo studies using NOD scid gamma mice and NRGS mice treated with 25 mg/mL busulfan, followed by weekly monitoring of disease burden through flow cytometry.
TAKEAWAY:
- CD37 surface expression was identified on all primary AML blasts examined, with varying levels of expression not correlating with European LeukemiaNet classification or overall survival.
- AML blasts demonstrated significantly higher CD37 internalization frequency than normal B cells (P = .001) and monocytes (P = .01), independent of surface expression levels.
- Primary AML samples with activating signaling mutations showed a trend toward increased CD37 internalization frequency (P = .053) than those without signaling mutations.
- Treatment with anti–CD37-DM1 significantly improved clinical outcomes and overall survival in multiple in vivo models of AML while showing minimal toxicity in humanized CD37 knockin mice.
IN PRACTICE:
“CD37 is a surface receptor present on most AML blasts, which has unique internalization properties when compared with normal blood cells. Treatment of AML with anti-CD37 ADC demonstrates specific cytotoxicity in vitro and improved overall survival in vivo,” wrote the authors of the study.
SOURCE:
The study was led by Erin Jeremy and Esthela Artiga, Ohio State University, Columbus. It was published online on January 14 in Blood Advances.
LIMITATIONS:
According to the authors, variations in CD37 expression in response to laboratory manipulations such as Ficoll-Hypaque cell separation and cryopreservation may have affected the detection of CD37 on AML cells with inherently lower levels of expression. The researchers also note that they were unable to associate pathologic characteristics with membrane trafficking and cytotoxic activity within their cohort of samples.
DISCLOSURES:
Karilyn T. Larkin received research funding from Debiopharm. The remaining authors reported no competing financial interests.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers analyzed CD37 expression in 55 untreated, newly diagnosed primary AML samples, along with normal hematopoietic stem cells, peripheral blood mononuclear cells, and AML cell lines.
- Analysis included internalization assays using anti-CD37 antibody conjugated to fluorochrome Alexa Fluor 647, with cells incubated for 2 hours at 37 °C vs on ice to quantify surface and intracellular CD37.
- Investigators conducted in vivo studies using NOD scid gamma mice and NRGS mice treated with 25 mg/mL busulfan, followed by weekly monitoring of disease burden through flow cytometry.
TAKEAWAY:
- CD37 surface expression was identified on all primary AML blasts examined, with varying levels of expression not correlating with European LeukemiaNet classification or overall survival.
- AML blasts demonstrated significantly higher CD37 internalization frequency than normal B cells (P = .001) and monocytes (P = .01), independent of surface expression levels.
- Primary AML samples with activating signaling mutations showed a trend toward increased CD37 internalization frequency (P = .053) than those without signaling mutations.
- Treatment with anti–CD37-DM1 significantly improved clinical outcomes and overall survival in multiple in vivo models of AML while showing minimal toxicity in humanized CD37 knockin mice.
IN PRACTICE:
“CD37 is a surface receptor present on most AML blasts, which has unique internalization properties when compared with normal blood cells. Treatment of AML with anti-CD37 ADC demonstrates specific cytotoxicity in vitro and improved overall survival in vivo,” wrote the authors of the study.
SOURCE:
The study was led by Erin Jeremy and Esthela Artiga, Ohio State University, Columbus. It was published online on January 14 in Blood Advances.
LIMITATIONS:
According to the authors, variations in CD37 expression in response to laboratory manipulations such as Ficoll-Hypaque cell separation and cryopreservation may have affected the detection of CD37 on AML cells with inherently lower levels of expression. The researchers also note that they were unable to associate pathologic characteristics with membrane trafficking and cytotoxic activity within their cohort of samples.
DISCLOSURES:
Karilyn T. Larkin received research funding from Debiopharm. The remaining authors reported no competing financial interests.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers analyzed CD37 expression in 55 untreated, newly diagnosed primary AML samples, along with normal hematopoietic stem cells, peripheral blood mononuclear cells, and AML cell lines.
- Analysis included internalization assays using anti-CD37 antibody conjugated to fluorochrome Alexa Fluor 647, with cells incubated for 2 hours at 37 °C vs on ice to quantify surface and intracellular CD37.
- Investigators conducted in vivo studies using NOD scid gamma mice and NRGS mice treated with 25 mg/mL busulfan, followed by weekly monitoring of disease burden through flow cytometry.
TAKEAWAY:
- CD37 surface expression was identified on all primary AML blasts examined, with varying levels of expression not correlating with European LeukemiaNet classification or overall survival.
- AML blasts demonstrated significantly higher CD37 internalization frequency than normal B cells (P = .001) and monocytes (P = .01), independent of surface expression levels.
- Primary AML samples with activating signaling mutations showed a trend toward increased CD37 internalization frequency (P = .053) than those without signaling mutations.
- Treatment with anti–CD37-DM1 significantly improved clinical outcomes and overall survival in multiple in vivo models of AML while showing minimal toxicity in humanized CD37 knockin mice.
IN PRACTICE:
“CD37 is a surface receptor present on most AML blasts, which has unique internalization properties when compared with normal blood cells. Treatment of AML with anti-CD37 ADC demonstrates specific cytotoxicity in vitro and improved overall survival in vivo,” wrote the authors of the study.
SOURCE:
The study was led by Erin Jeremy and Esthela Artiga, Ohio State University, Columbus. It was published online on January 14 in Blood Advances.
LIMITATIONS:
According to the authors, variations in CD37 expression in response to laboratory manipulations such as Ficoll-Hypaque cell separation and cryopreservation may have affected the detection of CD37 on AML cells with inherently lower levels of expression. The researchers also note that they were unable to associate pathologic characteristics with membrane trafficking and cytotoxic activity within their cohort of samples.
DISCLOSURES:
Karilyn T. Larkin received research funding from Debiopharm. The remaining authors reported no competing financial interests.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Myeloma: Can Failed Drugs Work Again?
TOPLINE:
METHODOLOGY:
- Researchers retrospectively reviewed patients with relapsed/refractory multiple myeloma who started new systemic therapy for disease progression between January 2015 and April 2022 at their institution.
- Analysis included 315 patients treated with a drug that their disease had previously been refractory to, defined as disease progression while receiving the drug or within 60 days of the last dose.
- Patient characteristics collected at diagnosis included age, sex, International Staging System stage, revised International Staging System stage, and interphase fluorescence in situ hybridization abnormalities.
- Investigators considered the first relapse after January 2015 requiring new systemic therapy as the index relapse and study start time.
TAKEAWAY:
- Analysis revealed an overall response rate of 56.2% and median progression-free survival of 11 months with retreatment.
- Patients with longer initial therapy duration with index drug (> 28.4 months) demonstrated superior progression-free survival (median, 16.9 vs 8.1 months; P < .001).
- Researchers found that patients with longer time gap between initial therapy and retreatment (> 46.1 months) showed better progression-free survival (median, 28.2 vs 8.9 months; P = .016).
- Among the 285 evaluable patients, 26% achieved partial response and 30.2% achieved very good partial response or better with retreatment.
IN PRACTICE:
“Retreatment with previously refractory drugs is a viable option for late-line [relapsed/refractory multiple myeloma]. Patients with a longer gap between initial line of therapy with index drug and retreatment had superior outcomes with retreatment,” wrote the authors of the study.
SOURCE:
The study was led by Utkarsh Goel, Division of Hematology, Mayo Clinic in Rochester, Minnesota. It was published online on December 24, 2024, in Blood Advances.
LIMITATIONS:
The retrospective nature and single-institution design of the study may introduce bias in terms of patient population and practice patterns. The favorable outcomes observed in patients with longer initial therapy duration and greater time between treatments could reflect selection bias toward more indolent disease biology. Despite adjusting for nonrefractory partner drugs during index relapse, residual bias may limit the ability to attribute outcomes solely to retreatment. The heterogeneous nature of treatments received during index relapse may limit comparisons across different groups.
DISCLOSURES:
Nelson Leung reported ties with AbbVie, Senseonics, Verrica Pharmaceuticals, and Omeros. Yi Lin disclosed relationships with multiple institutions, including Bristol Myers Squibb, Caribou Biosciences, and Janssen Oncology. Shaji Kumar reported ties with AbbVie, Bristol-Myers Squibb/Celgene, and Janssen Oncology. Additional disclosures were noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers retrospectively reviewed patients with relapsed/refractory multiple myeloma who started new systemic therapy for disease progression between January 2015 and April 2022 at their institution.
- Analysis included 315 patients treated with a drug that their disease had previously been refractory to, defined as disease progression while receiving the drug or within 60 days of the last dose.
- Patient characteristics collected at diagnosis included age, sex, International Staging System stage, revised International Staging System stage, and interphase fluorescence in situ hybridization abnormalities.
- Investigators considered the first relapse after January 2015 requiring new systemic therapy as the index relapse and study start time.
TAKEAWAY:
- Analysis revealed an overall response rate of 56.2% and median progression-free survival of 11 months with retreatment.
- Patients with longer initial therapy duration with index drug (> 28.4 months) demonstrated superior progression-free survival (median, 16.9 vs 8.1 months; P < .001).
- Researchers found that patients with longer time gap between initial therapy and retreatment (> 46.1 months) showed better progression-free survival (median, 28.2 vs 8.9 months; P = .016).
- Among the 285 evaluable patients, 26% achieved partial response and 30.2% achieved very good partial response or better with retreatment.
IN PRACTICE:
“Retreatment with previously refractory drugs is a viable option for late-line [relapsed/refractory multiple myeloma]. Patients with a longer gap between initial line of therapy with index drug and retreatment had superior outcomes with retreatment,” wrote the authors of the study.
SOURCE:
The study was led by Utkarsh Goel, Division of Hematology, Mayo Clinic in Rochester, Minnesota. It was published online on December 24, 2024, in Blood Advances.
LIMITATIONS:
The retrospective nature and single-institution design of the study may introduce bias in terms of patient population and practice patterns. The favorable outcomes observed in patients with longer initial therapy duration and greater time between treatments could reflect selection bias toward more indolent disease biology. Despite adjusting for nonrefractory partner drugs during index relapse, residual bias may limit the ability to attribute outcomes solely to retreatment. The heterogeneous nature of treatments received during index relapse may limit comparisons across different groups.
DISCLOSURES:
Nelson Leung reported ties with AbbVie, Senseonics, Verrica Pharmaceuticals, and Omeros. Yi Lin disclosed relationships with multiple institutions, including Bristol Myers Squibb, Caribou Biosciences, and Janssen Oncology. Shaji Kumar reported ties with AbbVie, Bristol-Myers Squibb/Celgene, and Janssen Oncology. Additional disclosures were noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers retrospectively reviewed patients with relapsed/refractory multiple myeloma who started new systemic therapy for disease progression between January 2015 and April 2022 at their institution.
- Analysis included 315 patients treated with a drug that their disease had previously been refractory to, defined as disease progression while receiving the drug or within 60 days of the last dose.
- Patient characteristics collected at diagnosis included age, sex, International Staging System stage, revised International Staging System stage, and interphase fluorescence in situ hybridization abnormalities.
- Investigators considered the first relapse after January 2015 requiring new systemic therapy as the index relapse and study start time.
TAKEAWAY:
- Analysis revealed an overall response rate of 56.2% and median progression-free survival of 11 months with retreatment.
- Patients with longer initial therapy duration with index drug (> 28.4 months) demonstrated superior progression-free survival (median, 16.9 vs 8.1 months; P < .001).
- Researchers found that patients with longer time gap between initial therapy and retreatment (> 46.1 months) showed better progression-free survival (median, 28.2 vs 8.9 months; P = .016).
- Among the 285 evaluable patients, 26% achieved partial response and 30.2% achieved very good partial response or better with retreatment.
IN PRACTICE:
“Retreatment with previously refractory drugs is a viable option for late-line [relapsed/refractory multiple myeloma]. Patients with a longer gap between initial line of therapy with index drug and retreatment had superior outcomes with retreatment,” wrote the authors of the study.
SOURCE:
The study was led by Utkarsh Goel, Division of Hematology, Mayo Clinic in Rochester, Minnesota. It was published online on December 24, 2024, in Blood Advances.
LIMITATIONS:
The retrospective nature and single-institution design of the study may introduce bias in terms of patient population and practice patterns. The favorable outcomes observed in patients with longer initial therapy duration and greater time between treatments could reflect selection bias toward more indolent disease biology. Despite adjusting for nonrefractory partner drugs during index relapse, residual bias may limit the ability to attribute outcomes solely to retreatment. The heterogeneous nature of treatments received during index relapse may limit comparisons across different groups.
DISCLOSURES:
Nelson Leung reported ties with AbbVie, Senseonics, Verrica Pharmaceuticals, and Omeros. Yi Lin disclosed relationships with multiple institutions, including Bristol Myers Squibb, Caribou Biosciences, and Janssen Oncology. Shaji Kumar reported ties with AbbVie, Bristol-Myers Squibb/Celgene, and Janssen Oncology. Additional disclosures were noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Can Glucarpidase Help Reverse Methotrexate Kidney Damage?
TOPLINE:
METHODOLOGY:
- Researchers conducted a multicenter cohort study involving 708 adults with methotrexate-associated acute kidney injury from 28 cancer centers across the United States.
- Analysis utilized a sequential target trial emulation framework to compare outcomes between 209 patients who received glucarpidase within 4 days of methotrexate initiation and 499 patients who did not.
- The primary endpoint was kidney recovery at hospital discharge, defined as survival with serum creatinine < 1.5-fold baseline without dialysis dependence.
- Secondary endpoints included time-to-kidney recovery, neutropenia and transaminitis on day 7, and time-to-death.
TAKEAWAY:
- Glucarpidase administration was associated with adjusted odds ratio [aOR] of 2.70 (95% CI, 1.69-4.31) and adjusted hazard ratio [aHR] of 1.88 (95% CI, 1.18-3.33) for time-to-kidney recovery.
- Treatment with glucarpidase reduced the risk for grade ≥ 2 neutropenia (aOR, 0.50; 95% CI, 0.28-0.91) and grade ≥ 2 transaminitis (aOR, 0.31; 95% CI, 0.13-0.77) on day 7.
- Female patients showed greater benefit from glucarpidase treatment than male patients (P = .02 for interaction).
- No significant difference was observed in time-to-death between glucarpidase-treated and glucarpidase-untreated patients (aHR, 0.76; 95% CI, 0.49-1.18).
IN PRACTICE:
“These data suggest glucarpidase may improve both renal and extrarenal outcomes in patients with MTX-AKI [methotrexate-acute kidney injury],” the authors of the study wrote.
SOURCE:
This study was led by Shruti Gupta, MD, MPH, and David E. Leaf, MD, MMSc, Brigham and Women’s Hospital in Boston, Massachusetts. It was published online in Blood.
LIMITATIONS:
According to the authors, residual confounding cannot be excluded despite adjustment for multiple variables. While glucarpidase-treated patients had similar distributions of most baseline characteristics, they showed greater severity of illness, including more comorbidities, concomitant nephrotoxic medications, higher 24-hour methotrexate levels, and more severe acute kidney injury. This study was limited to patients treated at large, US-based academic centers, potentially affecting generalizability to smaller hospitals or countries where glucarpidase is unavailable.
DISCLOSURES:
This study was funded by BTG International. Gupta disclosed ties with BTG International, Dana-Farber Cancer Institute’s Wong Foundation, Janssen, AstraZeneca, and the National Institute of Diabetes and Digestive and Kidney Diseases (K23DK125672). Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers conducted a multicenter cohort study involving 708 adults with methotrexate-associated acute kidney injury from 28 cancer centers across the United States.
- Analysis utilized a sequential target trial emulation framework to compare outcomes between 209 patients who received glucarpidase within 4 days of methotrexate initiation and 499 patients who did not.
- The primary endpoint was kidney recovery at hospital discharge, defined as survival with serum creatinine < 1.5-fold baseline without dialysis dependence.
- Secondary endpoints included time-to-kidney recovery, neutropenia and transaminitis on day 7, and time-to-death.
TAKEAWAY:
- Glucarpidase administration was associated with adjusted odds ratio [aOR] of 2.70 (95% CI, 1.69-4.31) and adjusted hazard ratio [aHR] of 1.88 (95% CI, 1.18-3.33) for time-to-kidney recovery.
- Treatment with glucarpidase reduced the risk for grade ≥ 2 neutropenia (aOR, 0.50; 95% CI, 0.28-0.91) and grade ≥ 2 transaminitis (aOR, 0.31; 95% CI, 0.13-0.77) on day 7.
- Female patients showed greater benefit from glucarpidase treatment than male patients (P = .02 for interaction).
- No significant difference was observed in time-to-death between glucarpidase-treated and glucarpidase-untreated patients (aHR, 0.76; 95% CI, 0.49-1.18).
IN PRACTICE:
“These data suggest glucarpidase may improve both renal and extrarenal outcomes in patients with MTX-AKI [methotrexate-acute kidney injury],” the authors of the study wrote.
SOURCE:
This study was led by Shruti Gupta, MD, MPH, and David E. Leaf, MD, MMSc, Brigham and Women’s Hospital in Boston, Massachusetts. It was published online in Blood.
LIMITATIONS:
According to the authors, residual confounding cannot be excluded despite adjustment for multiple variables. While glucarpidase-treated patients had similar distributions of most baseline characteristics, they showed greater severity of illness, including more comorbidities, concomitant nephrotoxic medications, higher 24-hour methotrexate levels, and more severe acute kidney injury. This study was limited to patients treated at large, US-based academic centers, potentially affecting generalizability to smaller hospitals or countries where glucarpidase is unavailable.
DISCLOSURES:
This study was funded by BTG International. Gupta disclosed ties with BTG International, Dana-Farber Cancer Institute’s Wong Foundation, Janssen, AstraZeneca, and the National Institute of Diabetes and Digestive and Kidney Diseases (K23DK125672). Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers conducted a multicenter cohort study involving 708 adults with methotrexate-associated acute kidney injury from 28 cancer centers across the United States.
- Analysis utilized a sequential target trial emulation framework to compare outcomes between 209 patients who received glucarpidase within 4 days of methotrexate initiation and 499 patients who did not.
- The primary endpoint was kidney recovery at hospital discharge, defined as survival with serum creatinine < 1.5-fold baseline without dialysis dependence.
- Secondary endpoints included time-to-kidney recovery, neutropenia and transaminitis on day 7, and time-to-death.
TAKEAWAY:
- Glucarpidase administration was associated with adjusted odds ratio [aOR] of 2.70 (95% CI, 1.69-4.31) and adjusted hazard ratio [aHR] of 1.88 (95% CI, 1.18-3.33) for time-to-kidney recovery.
- Treatment with glucarpidase reduced the risk for grade ≥ 2 neutropenia (aOR, 0.50; 95% CI, 0.28-0.91) and grade ≥ 2 transaminitis (aOR, 0.31; 95% CI, 0.13-0.77) on day 7.
- Female patients showed greater benefit from glucarpidase treatment than male patients (P = .02 for interaction).
- No significant difference was observed in time-to-death between glucarpidase-treated and glucarpidase-untreated patients (aHR, 0.76; 95% CI, 0.49-1.18).
IN PRACTICE:
“These data suggest glucarpidase may improve both renal and extrarenal outcomes in patients with MTX-AKI [methotrexate-acute kidney injury],” the authors of the study wrote.
SOURCE:
This study was led by Shruti Gupta, MD, MPH, and David E. Leaf, MD, MMSc, Brigham and Women’s Hospital in Boston, Massachusetts. It was published online in Blood.
LIMITATIONS:
According to the authors, residual confounding cannot be excluded despite adjustment for multiple variables. While glucarpidase-treated patients had similar distributions of most baseline characteristics, they showed greater severity of illness, including more comorbidities, concomitant nephrotoxic medications, higher 24-hour methotrexate levels, and more severe acute kidney injury. This study was limited to patients treated at large, US-based academic centers, potentially affecting generalizability to smaller hospitals or countries where glucarpidase is unavailable.
DISCLOSURES:
This study was funded by BTG International. Gupta disclosed ties with BTG International, Dana-Farber Cancer Institute’s Wong Foundation, Janssen, AstraZeneca, and the National Institute of Diabetes and Digestive and Kidney Diseases (K23DK125672). Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
SCD: Can Atrial Arrhythmias Predict Strokes?
TOPLINE:
METHODOLOGY:
- A total of 130 adult patients with SCD were included in the DREPACOEUR prospective registry from November 2018 to November 2022.
- The patients underwent a comprehensive cardiac evaluation, including 24-hour electrocardiogram monitoring, echocardiography, and laboratory tests.
- The primary endpoint was the occurrence of atrial arrhythmias, defined by excessive supraventricular ectopic activity or any recent history of atrial fibrillation.
- Patients with a history of stroke or transient ischemic attack were also included in the PCDREP prospective registry for further assessment.
- Written informed consent was collected from all participating patients, and the study was approved by the ethics committee.
TAKEAWAY:
- Atrial arrhythmias were found in 26% of patients with SCD, with a significant association with stroke history (P = .001).
- Age and left atrial volume were independently associated with atrial arrhythmias, with optimal cutoffs of 47 years and 55 mL/m2, respectively.
- Patients with atrial arrhythmias had higher diastolic blood pressure, worse kidney function, and higher NT pro-BNP levels than those without arrhythmias.
- Atrial arrhythmias were associated with an increased risk for stroke unrelated to cerebral vasculopathy or other defined causes (odds ratio, 6.6; P = .009).
“Atrial arrhythmias were found in 26% of patients with sickle cell anemia, with a significant association with stroke history,” wrote the authors of the study. In a commentary published concurrently, Jonathan Uniat, MD, of Children’s Hospital Los Angeles in California, wrote, “Early detection and treatment of atrial arrhythmias may help prevent strokes in this population.”
SOURCE:
The study was led by Thomas d’Humières, Henri Mondor Hospital in Créteil, France. It was published online on November 12 in Blood Advances.
LIMITATIONS:
This study was a pilot prospective study and was underpowered with atrial arrhythmias occurring in only 34 patients. The population was relatively old for sickle cell anemia (45 years), and the study was biased because patients were selected based on clinical criteria indicative of underlying cardiovascular abnormalities. The population was heterogeneous in terms of antiarrhythmic therapy, and overall, at an advanced stage of the disease with frequent organ complications.
DISCLOSURES:
The study was supported by grants from FHU-SENEC. Pablo Bartolucci received grants from Addmedica, the Fabre Foundation, Novartis, and Bluebird in the past 36 months; received consulting fees from Addmedica, Novartis, Roche, GBT, Bluebird, Emmaus, Hemanext, and Agios; received honoraria for lectures from Novartis, Addmedica, and Jazz Pharmaceuticals; and reported being a member of the Novartis steering committee and cofounder of Innovhem. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- A total of 130 adult patients with SCD were included in the DREPACOEUR prospective registry from November 2018 to November 2022.
- The patients underwent a comprehensive cardiac evaluation, including 24-hour electrocardiogram monitoring, echocardiography, and laboratory tests.
- The primary endpoint was the occurrence of atrial arrhythmias, defined by excessive supraventricular ectopic activity or any recent history of atrial fibrillation.
- Patients with a history of stroke or transient ischemic attack were also included in the PCDREP prospective registry for further assessment.
- Written informed consent was collected from all participating patients, and the study was approved by the ethics committee.
TAKEAWAY:
- Atrial arrhythmias were found in 26% of patients with SCD, with a significant association with stroke history (P = .001).
- Age and left atrial volume were independently associated with atrial arrhythmias, with optimal cutoffs of 47 years and 55 mL/m2, respectively.
- Patients with atrial arrhythmias had higher diastolic blood pressure, worse kidney function, and higher NT pro-BNP levels than those without arrhythmias.
- Atrial arrhythmias were associated with an increased risk for stroke unrelated to cerebral vasculopathy or other defined causes (odds ratio, 6.6; P = .009).
“Atrial arrhythmias were found in 26% of patients with sickle cell anemia, with a significant association with stroke history,” wrote the authors of the study. In a commentary published concurrently, Jonathan Uniat, MD, of Children’s Hospital Los Angeles in California, wrote, “Early detection and treatment of atrial arrhythmias may help prevent strokes in this population.”
SOURCE:
The study was led by Thomas d’Humières, Henri Mondor Hospital in Créteil, France. It was published online on November 12 in Blood Advances.
LIMITATIONS:
This study was a pilot prospective study and was underpowered with atrial arrhythmias occurring in only 34 patients. The population was relatively old for sickle cell anemia (45 years), and the study was biased because patients were selected based on clinical criteria indicative of underlying cardiovascular abnormalities. The population was heterogeneous in terms of antiarrhythmic therapy, and overall, at an advanced stage of the disease with frequent organ complications.
DISCLOSURES:
The study was supported by grants from FHU-SENEC. Pablo Bartolucci received grants from Addmedica, the Fabre Foundation, Novartis, and Bluebird in the past 36 months; received consulting fees from Addmedica, Novartis, Roche, GBT, Bluebird, Emmaus, Hemanext, and Agios; received honoraria for lectures from Novartis, Addmedica, and Jazz Pharmaceuticals; and reported being a member of the Novartis steering committee and cofounder of Innovhem. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- A total of 130 adult patients with SCD were included in the DREPACOEUR prospective registry from November 2018 to November 2022.
- The patients underwent a comprehensive cardiac evaluation, including 24-hour electrocardiogram monitoring, echocardiography, and laboratory tests.
- The primary endpoint was the occurrence of atrial arrhythmias, defined by excessive supraventricular ectopic activity or any recent history of atrial fibrillation.
- Patients with a history of stroke or transient ischemic attack were also included in the PCDREP prospective registry for further assessment.
- Written informed consent was collected from all participating patients, and the study was approved by the ethics committee.
TAKEAWAY:
- Atrial arrhythmias were found in 26% of patients with SCD, with a significant association with stroke history (P = .001).
- Age and left atrial volume were independently associated with atrial arrhythmias, with optimal cutoffs of 47 years and 55 mL/m2, respectively.
- Patients with atrial arrhythmias had higher diastolic blood pressure, worse kidney function, and higher NT pro-BNP levels than those without arrhythmias.
- Atrial arrhythmias were associated with an increased risk for stroke unrelated to cerebral vasculopathy or other defined causes (odds ratio, 6.6; P = .009).
“Atrial arrhythmias were found in 26% of patients with sickle cell anemia, with a significant association with stroke history,” wrote the authors of the study. In a commentary published concurrently, Jonathan Uniat, MD, of Children’s Hospital Los Angeles in California, wrote, “Early detection and treatment of atrial arrhythmias may help prevent strokes in this population.”
SOURCE:
The study was led by Thomas d’Humières, Henri Mondor Hospital in Créteil, France. It was published online on November 12 in Blood Advances.
LIMITATIONS:
This study was a pilot prospective study and was underpowered with atrial arrhythmias occurring in only 34 patients. The population was relatively old for sickle cell anemia (45 years), and the study was biased because patients were selected based on clinical criteria indicative of underlying cardiovascular abnormalities. The population was heterogeneous in terms of antiarrhythmic therapy, and overall, at an advanced stage of the disease with frequent organ complications.
DISCLOSURES:
The study was supported by grants from FHU-SENEC. Pablo Bartolucci received grants from Addmedica, the Fabre Foundation, Novartis, and Bluebird in the past 36 months; received consulting fees from Addmedica, Novartis, Roche, GBT, Bluebird, Emmaus, Hemanext, and Agios; received honoraria for lectures from Novartis, Addmedica, and Jazz Pharmaceuticals; and reported being a member of the Novartis steering committee and cofounder of Innovhem. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Venetoclax-Obinutuzumab: CLL’s New Power Duo?
TOPLINE:
METHODOLOGY:
- A total of 432 patients with previously untreated CLL and coexisting conditions were enrolled in the study.
- Participants were randomized 1:1 to receive either 12 cycles of venetoclax with 6 cycles of obinutuzumab or 12 cycles of chlorambucil with 6 cycles of obinutuzumab.
- The primary endpoint was PFS, with secondary endpoints including TTNT, overall survival (OS), and adverse events.
- Minimal residual disease was assessed in peripheral blood and bone marrow at the end of treatment and at several follow-up points.
- The study was conducted across multiple centers and was registered with clinical trial identifiers NCT02242942 and EudraCT 2014-001810-24.
TAKEAWAY:
- The 6-year PFS rate was significantly higher in the venetoclax-obinutuzumab group (53%) than in the chlorambucil-obinutuzumab group (21.7%) (P < .0001).
- The TTNT rate was 65.2% in the venetoclax-obinutuzumab group vs 37.1% in the chlorambucil-obinutuzumab group (P < .0001).
- The OS rate at 6 years was 78.7% in the venetoclax-obinutuzumab group and 69.2% in the chlorambucil-obinutuzumab group (P = .052).
- Patients in the venetoclax-obinutuzumab group reported better quality of life and less fatigue than those in the chlorambucil-obinutuzumab group.
IN PRACTICE:
“Patients treated with the venetoclax-obinutuzumab combination showed a statistically significant sustained prolongation of PFS, compared with patients treated with chlorambucil-obinutuzumab (76.2 vs 36.4 months). Overall, the PFS rate was 53% in the venetoclax-obinutuzumab group vs 21.7% after chlorambucil-obinutuzumab,” the study’s authors wrote.
In a related article, Silvia Deaglio, University of Turin in Italy, noted: “A second important observation of the study is that in the venetoclax-obinutuzumab arm, patients who relapsed more frequently presented with unmutated IGHV genes, deletion of 17p, or TP53 mutations.”
SOURCE:
This study was led by Othman Al-Sawaf, Sandra Robrecht, and Can Zhang, University of Cologne in Germany. It was published online on October 31 in Blood.
LIMITATIONS:
This study’s limitations included the relatively small sample size and the short duration of follow-up for some endpoints. Additionally, the study population was limited to older adult patients with coexisting conditions, which may limit the generalizability of the findings to a broader CLL population.
DISCLOSURES:
This study was supported by F. Hoffmann-La Roche and AbbVie. Al-Sawaf disclosed receiving grants from BeiGene, AbbVie, Janssen, and Roche. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- A total of 432 patients with previously untreated CLL and coexisting conditions were enrolled in the study.
- Participants were randomized 1:1 to receive either 12 cycles of venetoclax with 6 cycles of obinutuzumab or 12 cycles of chlorambucil with 6 cycles of obinutuzumab.
- The primary endpoint was PFS, with secondary endpoints including TTNT, overall survival (OS), and adverse events.
- Minimal residual disease was assessed in peripheral blood and bone marrow at the end of treatment and at several follow-up points.
- The study was conducted across multiple centers and was registered with clinical trial identifiers NCT02242942 and EudraCT 2014-001810-24.
TAKEAWAY:
- The 6-year PFS rate was significantly higher in the venetoclax-obinutuzumab group (53%) than in the chlorambucil-obinutuzumab group (21.7%) (P < .0001).
- The TTNT rate was 65.2% in the venetoclax-obinutuzumab group vs 37.1% in the chlorambucil-obinutuzumab group (P < .0001).
- The OS rate at 6 years was 78.7% in the venetoclax-obinutuzumab group and 69.2% in the chlorambucil-obinutuzumab group (P = .052).
- Patients in the venetoclax-obinutuzumab group reported better quality of life and less fatigue than those in the chlorambucil-obinutuzumab group.
IN PRACTICE:
“Patients treated with the venetoclax-obinutuzumab combination showed a statistically significant sustained prolongation of PFS, compared with patients treated with chlorambucil-obinutuzumab (76.2 vs 36.4 months). Overall, the PFS rate was 53% in the venetoclax-obinutuzumab group vs 21.7% after chlorambucil-obinutuzumab,” the study’s authors wrote.
In a related article, Silvia Deaglio, University of Turin in Italy, noted: “A second important observation of the study is that in the venetoclax-obinutuzumab arm, patients who relapsed more frequently presented with unmutated IGHV genes, deletion of 17p, or TP53 mutations.”
SOURCE:
This study was led by Othman Al-Sawaf, Sandra Robrecht, and Can Zhang, University of Cologne in Germany. It was published online on October 31 in Blood.
LIMITATIONS:
This study’s limitations included the relatively small sample size and the short duration of follow-up for some endpoints. Additionally, the study population was limited to older adult patients with coexisting conditions, which may limit the generalizability of the findings to a broader CLL population.
DISCLOSURES:
This study was supported by F. Hoffmann-La Roche and AbbVie. Al-Sawaf disclosed receiving grants from BeiGene, AbbVie, Janssen, and Roche. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- A total of 432 patients with previously untreated CLL and coexisting conditions were enrolled in the study.
- Participants were randomized 1:1 to receive either 12 cycles of venetoclax with 6 cycles of obinutuzumab or 12 cycles of chlorambucil with 6 cycles of obinutuzumab.
- The primary endpoint was PFS, with secondary endpoints including TTNT, overall survival (OS), and adverse events.
- Minimal residual disease was assessed in peripheral blood and bone marrow at the end of treatment and at several follow-up points.
- The study was conducted across multiple centers and was registered with clinical trial identifiers NCT02242942 and EudraCT 2014-001810-24.
TAKEAWAY:
- The 6-year PFS rate was significantly higher in the venetoclax-obinutuzumab group (53%) than in the chlorambucil-obinutuzumab group (21.7%) (P < .0001).
- The TTNT rate was 65.2% in the venetoclax-obinutuzumab group vs 37.1% in the chlorambucil-obinutuzumab group (P < .0001).
- The OS rate at 6 years was 78.7% in the venetoclax-obinutuzumab group and 69.2% in the chlorambucil-obinutuzumab group (P = .052).
- Patients in the venetoclax-obinutuzumab group reported better quality of life and less fatigue than those in the chlorambucil-obinutuzumab group.
IN PRACTICE:
“Patients treated with the venetoclax-obinutuzumab combination showed a statistically significant sustained prolongation of PFS, compared with patients treated with chlorambucil-obinutuzumab (76.2 vs 36.4 months). Overall, the PFS rate was 53% in the venetoclax-obinutuzumab group vs 21.7% after chlorambucil-obinutuzumab,” the study’s authors wrote.
In a related article, Silvia Deaglio, University of Turin in Italy, noted: “A second important observation of the study is that in the venetoclax-obinutuzumab arm, patients who relapsed more frequently presented with unmutated IGHV genes, deletion of 17p, or TP53 mutations.”
SOURCE:
This study was led by Othman Al-Sawaf, Sandra Robrecht, and Can Zhang, University of Cologne in Germany. It was published online on October 31 in Blood.
LIMITATIONS:
This study’s limitations included the relatively small sample size and the short duration of follow-up for some endpoints. Additionally, the study population was limited to older adult patients with coexisting conditions, which may limit the generalizability of the findings to a broader CLL population.
DISCLOSURES:
This study was supported by F. Hoffmann-La Roche and AbbVie. Al-Sawaf disclosed receiving grants from BeiGene, AbbVie, Janssen, and Roche. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Lung Cancer Expert at ASCO: From Fatal to ‘Chronic Disease’
After 20 years in Canada — 7 spent practicing community oncology near Toronto — Dr. Mok was visiting family in his native Hong Kong back in 1996 when a job offer there enabled him to revive his early dream of doing academic research. Dr. Mok and his family moved back home just before the former British colony was returned to China in 1997.
That leap of faith helped Dr. Mok play a role in the global paradigm shift on treating lung cancer. He chairs the department of clinical oncology at the Chinese University of Hong Kong. A leader in ushering in targeted therapies and personalized medicine in China and globally, he has helped advance the goal of transforming lung cancer from a death sentence to a chronic disease.
Among Dr. Mok’s other accomplishments, he has published eight books and more than 200 journal articles. Since 2006, he has been writing a twice-weekly column in the Hong Kong Economic Times. At the annual meeting of the American Society of Clinical Oncology (ASCO), Dr. Mok sat down with this news organization to discuss his latest findings, his career path, and China’s ever-growing presence in multinational clinical trials, pharmaceuticals, and cancer research in general.
Question: At ASCO 2024 in Chicago, you presented as first author of the KRYSTAL-12 study. Can you give a short “elevator speech” summarizing those findings?
Dr. Mok: KRYSTAL-12 is a randomized phase 3 study comparing adagrasib with docetaxel in patients with previously treated advanced/metastatic non–small cell lung cancer harboring a KRAS G12C-mutation. And the findings are positive, with a median progression free survival of 5.5 months vs 3.8 months, with a significant hazard ratio [of 0.58]. And then there are also differences in their response rates of 32% versus 9%, and that gives you an [odds] ratio of 4.86. So yes, it’s significant.
Question: Now that you’ve given this presentation and perhaps taken some good, meaningful questions about it, are there any further points you’d like to make — anything you’d like to add?
Dr. Mok: You have to understand that whatever I said has been scrutinized by the pharmaceutical company, but now I can say whatever I like. I think the key point is that we actually have made the first so-called achievement in the KRAS G12C space. But this is only the beginning.
I want to note that the median progression-free survival is different, but not the best. The median 5.5 months result is good, but not good enough. So, we still have to work hard to answer the question: How can we best deliver care to patients with KRAS G12C?
Question: Speaking more generally about the challenges of targeting KRAS, what issues arise in terms of biomarker testing for KRAS mutations in the clinic? Dr. Mok: In colorectal cancer, there has been testing for KRAS [mutations] for a long, long time. So, most of the laboratories, as long as they are well equipped, will be able to test for KRAS. Usually, the cheaper way is to buy PCR [polymerase chain reaction]. However, these days it’s getting trendier to use NGS [next-generation sequencing]. So, one way or another, specificity is very high. I don’t think we have too much of a problem. The only difference between colorectal cancer and lung cancer is that the tissue sample may not be as good for lung cancer with a small biopsy, but otherwise testing is not an issue.
Question: What clinical trials should oncologist be watching to come into this space?Dr. Mok: There are a lot. Right now, there is the so-called first-line study that’s coming up. So, I can cite you some examples for the KRYSTAL-7 trial, which is the combination of pembrolizumab together with adagrasib in the PD-L1 Tumor Proportion Score ≥ 50%.
That’s one example. And then there is the CodeBreaK 202 trial, which is actually the combination of chemotherapy with sotorasib versus chemotherapy and I-O [immune-oncology]. That is also an ongoing study.
Question: I also want to ask you some background questions about yourself. Back in the day, you lived in Canada and were a community oncologist. Then you made a very big change in your life and moved back home to Hong Kong in 1996, on the eve of its return to China the following year.
Dr. Mok: Well, I was born and raised in Hong Kong, but I left for Canada for education when I was 16 and kind of stayed there and got medical school oncology training and then started my practice. At that time, I never imagined myself going back. But 1996 was a big year. Incidentally, I went back to Hong Kong then to visit my friends and was offered a job at the Chinese University of Hong Kong. Then 1997 was coming. I found it very exciting that we could work with China. So that’s why I decided to return. And this was probably one of my best decisions I ever made in my life.
Question: And you went from being a community oncologist to academic research?
Dr. Mok: Here’s a personal thing that I can share with you: When I finished my oncology training at Princess Margaret Hospital in Toronto, I thought of going into research and becoming an academic. However, my son was born. Household costs went up, and I didn’t want to be a low-income, poor PhD student, so I decided that I may as well go into private practice. Returning to Hong Kong [in 1996] gave me a second chance. I went from being a community oncologist for seven years in Canada to a totally new environment in Hong Kong, where I started my academic work at age 36. It has been a good journey.
Question: Why do you say that was the best decision you ever made?Dr. Mok: At that time, it took me about 2 weeks to make this important decision. Basically: I had to give up my big house and my big car in Canada and move back to a small apartment in Hong Kong. That was a tough decision to make. However, it was a matter of certainty versus uncertainty.
In Canada, I actually had a very stable situation. I had a big practice in the Scarborough area [of Toronto], with a lot of Chinese patients, so I had a better, more comfortable life. It was predictable. But then I asked myself what I would be like in 10 years if I stayed in Canada versus Hong Kong. My answer is that I had no idea what would happen to me 10 years later in Hong Kong. In certain parts of life, you have to decide between certainty and uncertainty. And this time, uncertainty brought me great adventure. I definitely would not have done the things I’ve done if I’d stayed in Canada.
Question: At this ASCO, you’ve spoken primarily about your latest research on non–small cell lung cancer with KRAS G12C mutation.Dr. Mok: Actually, my research has been mostly on targeted therapy. My first break was on the EGFR [epidermal growth factor receptor] mutation. I was one of the first to help define personalized medicine according to the EGFR mutation in the IPASS study [2009]. That’s how I started my academic career.
Question: I read some quotes from your writing some years back about “living with imperfection,” and where you wrote about the whole continuum of cancer research. Years ago, you noted that lung cancer was moving from being a death sentence to becoming a chronic condition.
Dr. Mok: The objective is this: A lot of cancer patients, especially lung cancer patients, had a very short survival, but now we are able to identify a subgroup of patients with a driver oncogene.
And with that, we can use a tyrosine kinase inhibitor — which although it has toxicity, it’s manageable toxicity — such that you can take one pill a day and continue to live a normal life. So that would be not so different from diabetes or hypertension: You live with the disease. So that’s what we like to see: the conversion of a fatal disease into a chronic disease.
Question: So many countries now, including the United States and many others, are facing the challenges of cancer care in rural versus urban areas. Is this a topic you’d be willing to address? Dr. Mok: Well, in Hong Kong we don’t have rural areas! But in China, this is a major problem. There most of the cancer care is focused on the so-called three major cities [Shanghai, Beijing, Guangzhou]. And after that, there are second-tier cities that also have reasonably good care. But when you filter down to the third and fourth layer, the oncology care actually deteriorates. So that’s why we end up with a lot of people from the more rural areas moving and going to the city looking for care and consultation. So yes, the disparity is significant.
But China is a growing country. It takes time to change. Right now, we can see at ASCO this year, there are a lot of investigators from China sharing their new findings, which is a major development, compared to 10 years ago. Therefore, I think that when you have this type of proliferative development, eventually the good care, the high-quality care will filter down to more rural areas. So, at this moment, I think there is still a lot of work to do.
Question: You’ve talked about how oncologists from China are coming up in the field, and this year they have an even greater presence at ASCO, as well as oncologists from elsewhere in Asia, including South Korea, Japan, and Vietnam. You’ve been coming to ASCO for many years. Can you talk about the factors behind China’s increasing presence? Dr. Mok: I think it’s a combination of factors. First of all, I had the honor of working with lung cancer researchers from China from way back, 25 years ago. At that time, we all had nothing. Then with the development of multitargeted therapies, they managed to build up a very good infrastructure for clinical trials. And then, based on that good infrastructure, they were able to do international collaborative studies and provide a supply of patient resources and high-quality data. So, they’ve learned the trick, done a good job, but they cannot have so-called independence until there is a development of pharmaceuticals in China.
And then over the past 10 years, there’s been a proliferation — actually an explosion I would even say — of high-quality pharmaceutical companies in China. First, they’ve got the resources to build the companies. Second, they’ve got the talent resources returning from the United States. So, putting all that together, these were able to go from start-ups to full-fledged functional companies in a very short time.
And with that, they actually sponsored a lot of trials within China. And you can see that putting all the components together: you’ve got high-quality researchers, you’ve got the infrastructure, and now you’ve got your drugs and the money to do the trials. As a result, you’ve got a lot of good data coming from China.
Question: There’s also a population with these mutations.Dr. Mok: That for one, but most have multitargeted therapies, but they also have immunotherapies that have nothing to do with the high incidence. But I think in a sense, in the beginning, they were doing `me-too’ compounds, but now I think they are starting to do ‘me-better’ compounds.
Question: Is there anything you want to say about some of the other presentations that have your name on them at ASCO this year?Dr. Mok: I think the most important one I was engaged in is the CROWN study. The CROWN study is actually a phase 3 study that compares lorlatinib versus crizotinib in patients with advanced, ALK-positive non–small cell lung cancer.
This is a 5-year follow-up, and we were actually able to report an outrageously encouraging 5-year progression-free rate at 60%, meaning that the patient is walking in the door 5 years later when they are on the drug, and 60% of them actually do not have progression, not death, just not progression, just staying on the same pill—which is quite outrageously good for lung cancer.
After 20 years in Canada — 7 spent practicing community oncology near Toronto — Dr. Mok was visiting family in his native Hong Kong back in 1996 when a job offer there enabled him to revive his early dream of doing academic research. Dr. Mok and his family moved back home just before the former British colony was returned to China in 1997.
That leap of faith helped Dr. Mok play a role in the global paradigm shift on treating lung cancer. He chairs the department of clinical oncology at the Chinese University of Hong Kong. A leader in ushering in targeted therapies and personalized medicine in China and globally, he has helped advance the goal of transforming lung cancer from a death sentence to a chronic disease.
Among Dr. Mok’s other accomplishments, he has published eight books and more than 200 journal articles. Since 2006, he has been writing a twice-weekly column in the Hong Kong Economic Times. At the annual meeting of the American Society of Clinical Oncology (ASCO), Dr. Mok sat down with this news organization to discuss his latest findings, his career path, and China’s ever-growing presence in multinational clinical trials, pharmaceuticals, and cancer research in general.
Question: At ASCO 2024 in Chicago, you presented as first author of the KRYSTAL-12 study. Can you give a short “elevator speech” summarizing those findings?
Dr. Mok: KRYSTAL-12 is a randomized phase 3 study comparing adagrasib with docetaxel in patients with previously treated advanced/metastatic non–small cell lung cancer harboring a KRAS G12C-mutation. And the findings are positive, with a median progression free survival of 5.5 months vs 3.8 months, with a significant hazard ratio [of 0.58]. And then there are also differences in their response rates of 32% versus 9%, and that gives you an [odds] ratio of 4.86. So yes, it’s significant.
Question: Now that you’ve given this presentation and perhaps taken some good, meaningful questions about it, are there any further points you’d like to make — anything you’d like to add?
Dr. Mok: You have to understand that whatever I said has been scrutinized by the pharmaceutical company, but now I can say whatever I like. I think the key point is that we actually have made the first so-called achievement in the KRAS G12C space. But this is only the beginning.
I want to note that the median progression-free survival is different, but not the best. The median 5.5 months result is good, but not good enough. So, we still have to work hard to answer the question: How can we best deliver care to patients with KRAS G12C?
Question: Speaking more generally about the challenges of targeting KRAS, what issues arise in terms of biomarker testing for KRAS mutations in the clinic? Dr. Mok: In colorectal cancer, there has been testing for KRAS [mutations] for a long, long time. So, most of the laboratories, as long as they are well equipped, will be able to test for KRAS. Usually, the cheaper way is to buy PCR [polymerase chain reaction]. However, these days it’s getting trendier to use NGS [next-generation sequencing]. So, one way or another, specificity is very high. I don’t think we have too much of a problem. The only difference between colorectal cancer and lung cancer is that the tissue sample may not be as good for lung cancer with a small biopsy, but otherwise testing is not an issue.
Question: What clinical trials should oncologist be watching to come into this space?Dr. Mok: There are a lot. Right now, there is the so-called first-line study that’s coming up. So, I can cite you some examples for the KRYSTAL-7 trial, which is the combination of pembrolizumab together with adagrasib in the PD-L1 Tumor Proportion Score ≥ 50%.
That’s one example. And then there is the CodeBreaK 202 trial, which is actually the combination of chemotherapy with sotorasib versus chemotherapy and I-O [immune-oncology]. That is also an ongoing study.
Question: I also want to ask you some background questions about yourself. Back in the day, you lived in Canada and were a community oncologist. Then you made a very big change in your life and moved back home to Hong Kong in 1996, on the eve of its return to China the following year.
Dr. Mok: Well, I was born and raised in Hong Kong, but I left for Canada for education when I was 16 and kind of stayed there and got medical school oncology training and then started my practice. At that time, I never imagined myself going back. But 1996 was a big year. Incidentally, I went back to Hong Kong then to visit my friends and was offered a job at the Chinese University of Hong Kong. Then 1997 was coming. I found it very exciting that we could work with China. So that’s why I decided to return. And this was probably one of my best decisions I ever made in my life.
Question: And you went from being a community oncologist to academic research?
Dr. Mok: Here’s a personal thing that I can share with you: When I finished my oncology training at Princess Margaret Hospital in Toronto, I thought of going into research and becoming an academic. However, my son was born. Household costs went up, and I didn’t want to be a low-income, poor PhD student, so I decided that I may as well go into private practice. Returning to Hong Kong [in 1996] gave me a second chance. I went from being a community oncologist for seven years in Canada to a totally new environment in Hong Kong, where I started my academic work at age 36. It has been a good journey.
Question: Why do you say that was the best decision you ever made?Dr. Mok: At that time, it took me about 2 weeks to make this important decision. Basically: I had to give up my big house and my big car in Canada and move back to a small apartment in Hong Kong. That was a tough decision to make. However, it was a matter of certainty versus uncertainty.
In Canada, I actually had a very stable situation. I had a big practice in the Scarborough area [of Toronto], with a lot of Chinese patients, so I had a better, more comfortable life. It was predictable. But then I asked myself what I would be like in 10 years if I stayed in Canada versus Hong Kong. My answer is that I had no idea what would happen to me 10 years later in Hong Kong. In certain parts of life, you have to decide between certainty and uncertainty. And this time, uncertainty brought me great adventure. I definitely would not have done the things I’ve done if I’d stayed in Canada.
Question: At this ASCO, you’ve spoken primarily about your latest research on non–small cell lung cancer with KRAS G12C mutation.Dr. Mok: Actually, my research has been mostly on targeted therapy. My first break was on the EGFR [epidermal growth factor receptor] mutation. I was one of the first to help define personalized medicine according to the EGFR mutation in the IPASS study [2009]. That’s how I started my academic career.
Question: I read some quotes from your writing some years back about “living with imperfection,” and where you wrote about the whole continuum of cancer research. Years ago, you noted that lung cancer was moving from being a death sentence to becoming a chronic condition.
Dr. Mok: The objective is this: A lot of cancer patients, especially lung cancer patients, had a very short survival, but now we are able to identify a subgroup of patients with a driver oncogene.
And with that, we can use a tyrosine kinase inhibitor — which although it has toxicity, it’s manageable toxicity — such that you can take one pill a day and continue to live a normal life. So that would be not so different from diabetes or hypertension: You live with the disease. So that’s what we like to see: the conversion of a fatal disease into a chronic disease.
Question: So many countries now, including the United States and many others, are facing the challenges of cancer care in rural versus urban areas. Is this a topic you’d be willing to address? Dr. Mok: Well, in Hong Kong we don’t have rural areas! But in China, this is a major problem. There most of the cancer care is focused on the so-called three major cities [Shanghai, Beijing, Guangzhou]. And after that, there are second-tier cities that also have reasonably good care. But when you filter down to the third and fourth layer, the oncology care actually deteriorates. So that’s why we end up with a lot of people from the more rural areas moving and going to the city looking for care and consultation. So yes, the disparity is significant.
But China is a growing country. It takes time to change. Right now, we can see at ASCO this year, there are a lot of investigators from China sharing their new findings, which is a major development, compared to 10 years ago. Therefore, I think that when you have this type of proliferative development, eventually the good care, the high-quality care will filter down to more rural areas. So, at this moment, I think there is still a lot of work to do.
Question: You’ve talked about how oncologists from China are coming up in the field, and this year they have an even greater presence at ASCO, as well as oncologists from elsewhere in Asia, including South Korea, Japan, and Vietnam. You’ve been coming to ASCO for many years. Can you talk about the factors behind China’s increasing presence? Dr. Mok: I think it’s a combination of factors. First of all, I had the honor of working with lung cancer researchers from China from way back, 25 years ago. At that time, we all had nothing. Then with the development of multitargeted therapies, they managed to build up a very good infrastructure for clinical trials. And then, based on that good infrastructure, they were able to do international collaborative studies and provide a supply of patient resources and high-quality data. So, they’ve learned the trick, done a good job, but they cannot have so-called independence until there is a development of pharmaceuticals in China.
And then over the past 10 years, there’s been a proliferation — actually an explosion I would even say — of high-quality pharmaceutical companies in China. First, they’ve got the resources to build the companies. Second, they’ve got the talent resources returning from the United States. So, putting all that together, these were able to go from start-ups to full-fledged functional companies in a very short time.
And with that, they actually sponsored a lot of trials within China. And you can see that putting all the components together: you’ve got high-quality researchers, you’ve got the infrastructure, and now you’ve got your drugs and the money to do the trials. As a result, you’ve got a lot of good data coming from China.
Question: There’s also a population with these mutations.Dr. Mok: That for one, but most have multitargeted therapies, but they also have immunotherapies that have nothing to do with the high incidence. But I think in a sense, in the beginning, they were doing `me-too’ compounds, but now I think they are starting to do ‘me-better’ compounds.
Question: Is there anything you want to say about some of the other presentations that have your name on them at ASCO this year?Dr. Mok: I think the most important one I was engaged in is the CROWN study. The CROWN study is actually a phase 3 study that compares lorlatinib versus crizotinib in patients with advanced, ALK-positive non–small cell lung cancer.
This is a 5-year follow-up, and we were actually able to report an outrageously encouraging 5-year progression-free rate at 60%, meaning that the patient is walking in the door 5 years later when they are on the drug, and 60% of them actually do not have progression, not death, just not progression, just staying on the same pill—which is quite outrageously good for lung cancer.
After 20 years in Canada — 7 spent practicing community oncology near Toronto — Dr. Mok was visiting family in his native Hong Kong back in 1996 when a job offer there enabled him to revive his early dream of doing academic research. Dr. Mok and his family moved back home just before the former British colony was returned to China in 1997.
That leap of faith helped Dr. Mok play a role in the global paradigm shift on treating lung cancer. He chairs the department of clinical oncology at the Chinese University of Hong Kong. A leader in ushering in targeted therapies and personalized medicine in China and globally, he has helped advance the goal of transforming lung cancer from a death sentence to a chronic disease.
Among Dr. Mok’s other accomplishments, he has published eight books and more than 200 journal articles. Since 2006, he has been writing a twice-weekly column in the Hong Kong Economic Times. At the annual meeting of the American Society of Clinical Oncology (ASCO), Dr. Mok sat down with this news organization to discuss his latest findings, his career path, and China’s ever-growing presence in multinational clinical trials, pharmaceuticals, and cancer research in general.
Question: At ASCO 2024 in Chicago, you presented as first author of the KRYSTAL-12 study. Can you give a short “elevator speech” summarizing those findings?
Dr. Mok: KRYSTAL-12 is a randomized phase 3 study comparing adagrasib with docetaxel in patients with previously treated advanced/metastatic non–small cell lung cancer harboring a KRAS G12C-mutation. And the findings are positive, with a median progression free survival of 5.5 months vs 3.8 months, with a significant hazard ratio [of 0.58]. And then there are also differences in their response rates of 32% versus 9%, and that gives you an [odds] ratio of 4.86. So yes, it’s significant.
Question: Now that you’ve given this presentation and perhaps taken some good, meaningful questions about it, are there any further points you’d like to make — anything you’d like to add?
Dr. Mok: You have to understand that whatever I said has been scrutinized by the pharmaceutical company, but now I can say whatever I like. I think the key point is that we actually have made the first so-called achievement in the KRAS G12C space. But this is only the beginning.
I want to note that the median progression-free survival is different, but not the best. The median 5.5 months result is good, but not good enough. So, we still have to work hard to answer the question: How can we best deliver care to patients with KRAS G12C?
Question: Speaking more generally about the challenges of targeting KRAS, what issues arise in terms of biomarker testing for KRAS mutations in the clinic? Dr. Mok: In colorectal cancer, there has been testing for KRAS [mutations] for a long, long time. So, most of the laboratories, as long as they are well equipped, will be able to test for KRAS. Usually, the cheaper way is to buy PCR [polymerase chain reaction]. However, these days it’s getting trendier to use NGS [next-generation sequencing]. So, one way or another, specificity is very high. I don’t think we have too much of a problem. The only difference between colorectal cancer and lung cancer is that the tissue sample may not be as good for lung cancer with a small biopsy, but otherwise testing is not an issue.
Question: What clinical trials should oncologist be watching to come into this space?Dr. Mok: There are a lot. Right now, there is the so-called first-line study that’s coming up. So, I can cite you some examples for the KRYSTAL-7 trial, which is the combination of pembrolizumab together with adagrasib in the PD-L1 Tumor Proportion Score ≥ 50%.
That’s one example. And then there is the CodeBreaK 202 trial, which is actually the combination of chemotherapy with sotorasib versus chemotherapy and I-O [immune-oncology]. That is also an ongoing study.
Question: I also want to ask you some background questions about yourself. Back in the day, you lived in Canada and were a community oncologist. Then you made a very big change in your life and moved back home to Hong Kong in 1996, on the eve of its return to China the following year.
Dr. Mok: Well, I was born and raised in Hong Kong, but I left for Canada for education when I was 16 and kind of stayed there and got medical school oncology training and then started my practice. At that time, I never imagined myself going back. But 1996 was a big year. Incidentally, I went back to Hong Kong then to visit my friends and was offered a job at the Chinese University of Hong Kong. Then 1997 was coming. I found it very exciting that we could work with China. So that’s why I decided to return. And this was probably one of my best decisions I ever made in my life.
Question: And you went from being a community oncologist to academic research?
Dr. Mok: Here’s a personal thing that I can share with you: When I finished my oncology training at Princess Margaret Hospital in Toronto, I thought of going into research and becoming an academic. However, my son was born. Household costs went up, and I didn’t want to be a low-income, poor PhD student, so I decided that I may as well go into private practice. Returning to Hong Kong [in 1996] gave me a second chance. I went from being a community oncologist for seven years in Canada to a totally new environment in Hong Kong, where I started my academic work at age 36. It has been a good journey.
Question: Why do you say that was the best decision you ever made?Dr. Mok: At that time, it took me about 2 weeks to make this important decision. Basically: I had to give up my big house and my big car in Canada and move back to a small apartment in Hong Kong. That was a tough decision to make. However, it was a matter of certainty versus uncertainty.
In Canada, I actually had a very stable situation. I had a big practice in the Scarborough area [of Toronto], with a lot of Chinese patients, so I had a better, more comfortable life. It was predictable. But then I asked myself what I would be like in 10 years if I stayed in Canada versus Hong Kong. My answer is that I had no idea what would happen to me 10 years later in Hong Kong. In certain parts of life, you have to decide between certainty and uncertainty. And this time, uncertainty brought me great adventure. I definitely would not have done the things I’ve done if I’d stayed in Canada.
Question: At this ASCO, you’ve spoken primarily about your latest research on non–small cell lung cancer with KRAS G12C mutation.Dr. Mok: Actually, my research has been mostly on targeted therapy. My first break was on the EGFR [epidermal growth factor receptor] mutation. I was one of the first to help define personalized medicine according to the EGFR mutation in the IPASS study [2009]. That’s how I started my academic career.
Question: I read some quotes from your writing some years back about “living with imperfection,” and where you wrote about the whole continuum of cancer research. Years ago, you noted that lung cancer was moving from being a death sentence to becoming a chronic condition.
Dr. Mok: The objective is this: A lot of cancer patients, especially lung cancer patients, had a very short survival, but now we are able to identify a subgroup of patients with a driver oncogene.
And with that, we can use a tyrosine kinase inhibitor — which although it has toxicity, it’s manageable toxicity — such that you can take one pill a day and continue to live a normal life. So that would be not so different from diabetes or hypertension: You live with the disease. So that’s what we like to see: the conversion of a fatal disease into a chronic disease.
Question: So many countries now, including the United States and many others, are facing the challenges of cancer care in rural versus urban areas. Is this a topic you’d be willing to address? Dr. Mok: Well, in Hong Kong we don’t have rural areas! But in China, this is a major problem. There most of the cancer care is focused on the so-called three major cities [Shanghai, Beijing, Guangzhou]. And after that, there are second-tier cities that also have reasonably good care. But when you filter down to the third and fourth layer, the oncology care actually deteriorates. So that’s why we end up with a lot of people from the more rural areas moving and going to the city looking for care and consultation. So yes, the disparity is significant.
But China is a growing country. It takes time to change. Right now, we can see at ASCO this year, there are a lot of investigators from China sharing their new findings, which is a major development, compared to 10 years ago. Therefore, I think that when you have this type of proliferative development, eventually the good care, the high-quality care will filter down to more rural areas. So, at this moment, I think there is still a lot of work to do.
Question: You’ve talked about how oncologists from China are coming up in the field, and this year they have an even greater presence at ASCO, as well as oncologists from elsewhere in Asia, including South Korea, Japan, and Vietnam. You’ve been coming to ASCO for many years. Can you talk about the factors behind China’s increasing presence? Dr. Mok: I think it’s a combination of factors. First of all, I had the honor of working with lung cancer researchers from China from way back, 25 years ago. At that time, we all had nothing. Then with the development of multitargeted therapies, they managed to build up a very good infrastructure for clinical trials. And then, based on that good infrastructure, they were able to do international collaborative studies and provide a supply of patient resources and high-quality data. So, they’ve learned the trick, done a good job, but they cannot have so-called independence until there is a development of pharmaceuticals in China.
And then over the past 10 years, there’s been a proliferation — actually an explosion I would even say — of high-quality pharmaceutical companies in China. First, they’ve got the resources to build the companies. Second, they’ve got the talent resources returning from the United States. So, putting all that together, these were able to go from start-ups to full-fledged functional companies in a very short time.
And with that, they actually sponsored a lot of trials within China. And you can see that putting all the components together: you’ve got high-quality researchers, you’ve got the infrastructure, and now you’ve got your drugs and the money to do the trials. As a result, you’ve got a lot of good data coming from China.
Question: There’s also a population with these mutations.Dr. Mok: That for one, but most have multitargeted therapies, but they also have immunotherapies that have nothing to do with the high incidence. But I think in a sense, in the beginning, they were doing `me-too’ compounds, but now I think they are starting to do ‘me-better’ compounds.
Question: Is there anything you want to say about some of the other presentations that have your name on them at ASCO this year?Dr. Mok: I think the most important one I was engaged in is the CROWN study. The CROWN study is actually a phase 3 study that compares lorlatinib versus crizotinib in patients with advanced, ALK-positive non–small cell lung cancer.
This is a 5-year follow-up, and we were actually able to report an outrageously encouraging 5-year progression-free rate at 60%, meaning that the patient is walking in the door 5 years later when they are on the drug, and 60% of them actually do not have progression, not death, just not progression, just staying on the same pill—which is quite outrageously good for lung cancer.
FROM ASCO 2024