B Cell Lymphoma

Key clinical point: Compared with polatuzumab vedotin+bendamustine+rituximab (pola-BR) and rituximab+lenalidomide (R2), tafasitamab+lenalidomide provided a significant survival benefit in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Major finding: A significant overall survival (OS) benefit was observed with tafasitamab+lenalidomide vs pola-BR (hazard ratio [HR] 0.441; P = .034) and R2 (HR 0.435; P = .012). However, the OS was similar between the tafasitamab+lenalidomide and CD19-chimeric antigen receptor T-cell groups (CAR-T; HR 0.953; P = .892).

Study details: This expanded analysis of the RE-MIND2 study of propensity score-matched transplant-ineligible patients with R/R DLBCL treated with ≥2 systemic therapies who received tafasitamab+lenalidomide in the L-MIND trial and those who received pola-BR (24 pairs), R2 (33 pairs), or CAR-T (37 pairs) from an observational cohort.

Disclosures: This study was sponsored by MorphoSys AG. Some authors declared serving as consultants, advisory board members, or speakers and receiving research funding, honoraria, or travel support from MorphoSys and others. Four authors declared being employees of or holding equities in MorphoSys.

Source: Nowakowski GS et al. RE-MIND2: Comparative effectiveness of tafasitamab plus lenalidomide versus polatuzumab vedotin/bendamustine/rituximab (pola‑BR), CAR‑T therapies, and lenalidomide/rituximab (R2) based on real‑world data in patients with relapsed/refractory diffuse large B‑cell lymphoma. Ann Hematol. 2023;102:1773-1787 (May 12). doi: 10.1007/s00277-023-05196-4

Key clinical point: Compared with polatuzumab vedotin+bendamustine+rituximab (pola-BR) and rituximab+lenalidomide (R2), tafasitamab+lenalidomide provided a significant survival benefit in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Major finding: A significant overall survival (OS) benefit was observed with tafasitamab+lenalidomide vs pola-BR (hazard ratio [HR] 0.441; P = .034) and R2 (HR 0.435; P = .012). However, the OS was similar between the tafasitamab+lenalidomide and CD19-chimeric antigen receptor T-cell groups (CAR-T; HR 0.953; P = .892).

Study details: This expanded analysis of the RE-MIND2 study of propensity score-matched transplant-ineligible patients with R/R DLBCL treated with ≥2 systemic therapies who received tafasitamab+lenalidomide in the L-MIND trial and those who received pola-BR (24 pairs), R2 (33 pairs), or CAR-T (37 pairs) from an observational cohort.

Disclosures: This study was sponsored by MorphoSys AG. Some authors declared serving as consultants, advisory board members, or speakers and receiving research funding, honoraria, or travel support from MorphoSys and others. Four authors declared being employees of or holding equities in MorphoSys.

Source: Nowakowski GS et al. RE-MIND2: Comparative effectiveness of tafasitamab plus lenalidomide versus polatuzumab vedotin/bendamustine/rituximab (pola‑BR), CAR‑T therapies, and lenalidomide/rituximab (R2) based on real‑world data in patients with relapsed/refractory diffuse large B‑cell lymphoma. Ann Hematol. 2023;102:1773-1787 (May 12). doi: 10.1007/s00277-023-05196-4

Key clinical point: Compared with polatuzumab vedotin+bendamustine+rituximab (pola-BR) and rituximab+lenalidomide (R2), tafasitamab+lenalidomide provided a significant survival benefit in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Major finding: A significant overall survival (OS) benefit was observed with tafasitamab+lenalidomide vs pola-BR (hazard ratio [HR] 0.441; P = .034) and R2 (HR 0.435; P = .012). However, the OS was similar between the tafasitamab+lenalidomide and CD19-chimeric antigen receptor T-cell groups (CAR-T; HR 0.953; P = .892).

Study details: This expanded analysis of the RE-MIND2 study of propensity score-matched transplant-ineligible patients with R/R DLBCL treated with ≥2 systemic therapies who received tafasitamab+lenalidomide in the L-MIND trial and those who received pola-BR (24 pairs), R2 (33 pairs), or CAR-T (37 pairs) from an observational cohort.

Disclosures: This study was sponsored by MorphoSys AG. Some authors declared serving as consultants, advisory board members, or speakers and receiving research funding, honoraria, or travel support from MorphoSys and others. Four authors declared being employees of or holding equities in MorphoSys.

Source: Nowakowski GS et al. RE-MIND2: Comparative effectiveness of tafasitamab plus lenalidomide versus polatuzumab vedotin/bendamustine/rituximab (pola‑BR), CAR‑T therapies, and lenalidomide/rituximab (R2) based on real‑world data in patients with relapsed/refractory diffuse large B‑cell lymphoma. Ann Hematol. 2023;102:1773-1787 (May 12). doi: 10.1007/s00277-023-05196-4

Key clinical point: The rituximab, bendamustine, and low-dose cytarabine (R-BAC) regimen, not succeeded by maintenance therapy, induces long-term responses in previously untreated elderly patients with mantle cell lymphoma (MCL).

Major finding: After a median follow-up of 86 months, the median overall survival (OS) and progression-free survival (PFS) were not reached; the 7-year PFS and OS rates were 55% (95% CI 41%-67%) and 63% (95% CI 49%-74%), respectively. The 7-year duration of response rate among the 52 responding patients was 59% (95% CI 44%-71%). No signal of late toxicity was reported.

Study details: Findings are from a long-term analysis of the FIL-RBAC500 trial that included 57 previously untreated elderly patients with MCL who received the R-BAC regimen.

Disclosures: This study was supported by Progetto di Ricerca Sanitaria Finalizzata (Italy) grants and other sources. Some authors declared serving as advisory board members or consultants and receiving research funding, speaker honoraria, or travel expenses and accommodations from various sources.

Source: Tisi MC et al. Long term follow-up of rituximab plus bendamustine and cytarabine (R-BAC) in elderly patients with newly diagnosed MCL. Blood Adv. 2023 (May 12). doi: 10.1182/bloodadvances.2023009744

Key clinical point: The rituximab, bendamustine, and low-dose cytarabine (R-BAC) regimen, not succeeded by maintenance therapy, induces long-term responses in previously untreated elderly patients with mantle cell lymphoma (MCL).

Major finding: After a median follow-up of 86 months, the median overall survival (OS) and progression-free survival (PFS) were not reached; the 7-year PFS and OS rates were 55% (95% CI 41%-67%) and 63% (95% CI 49%-74%), respectively. The 7-year duration of response rate among the 52 responding patients was 59% (95% CI 44%-71%). No signal of late toxicity was reported.

Study details: Findings are from a long-term analysis of the FIL-RBAC500 trial that included 57 previously untreated elderly patients with MCL who received the R-BAC regimen.

Disclosures: This study was supported by Progetto di Ricerca Sanitaria Finalizzata (Italy) grants and other sources. Some authors declared serving as advisory board members or consultants and receiving research funding, speaker honoraria, or travel expenses and accommodations from various sources.

Source: Tisi MC et al. Long term follow-up of rituximab plus bendamustine and cytarabine (R-BAC) in elderly patients with newly diagnosed MCL. Blood Adv. 2023 (May 12). doi: 10.1182/bloodadvances.2023009744

Key clinical point: The rituximab, bendamustine, and low-dose cytarabine (R-BAC) regimen, not succeeded by maintenance therapy, induces long-term responses in previously untreated elderly patients with mantle cell lymphoma (MCL).

Major finding: After a median follow-up of 86 months, the median overall survival (OS) and progression-free survival (PFS) were not reached; the 7-year PFS and OS rates were 55% (95% CI 41%-67%) and 63% (95% CI 49%-74%), respectively. The 7-year duration of response rate among the 52 responding patients was 59% (95% CI 44%-71%). No signal of late toxicity was reported.

Study details: Findings are from a long-term analysis of the FIL-RBAC500 trial that included 57 previously untreated elderly patients with MCL who received the R-BAC regimen.

Disclosures: This study was supported by Progetto di Ricerca Sanitaria Finalizzata (Italy) grants and other sources. Some authors declared serving as advisory board members or consultants and receiving research funding, speaker honoraria, or travel expenses and accommodations from various sources.

Source: Tisi MC et al. Long term follow-up of rituximab plus bendamustine and cytarabine (R-BAC) in elderly patients with newly diagnosed MCL. Blood Adv. 2023 (May 12). doi: 10.1182/bloodadvances.2023009744

Key clinical point: First-line ibrutinib+venetoclax led to high response and survival rates in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) regardless of high-risk genomic features generally associated with poor outcomes.

Major finding: Overall response and 36-month overall survival rates were >95% regardless of high-risk features. Patients with and without high-risk features had similar complete response (61% [95% CI 53%-70%] and 53% [95% CI 41%-65%], respectively) and 36-month progression-free survival (88% [95% CI 81%-93%] and 92% [95% CI 82%-97%], respectively) rates.

Study details: This post hoc analysis of the CAPTIVATE trial analyzed the pooled data of 195 patients with previously untreated CLL/SLL and known status of high-risk features [del(17p), TP53 mutation, and unmutated immunoglobulin heavy chain] treated with fixed-duration ibrutinib+venetoclax, of which 129 had ≥1 high-risk feature.

Disclosures: This study was funded by Pharmacyclics LLC, an AbbVie Company. Some authors declared receiving grants, personal fees, or other support from Pharmacyclics, AbbVie, or others. Two authors declared being employees of Pharmacyclics or AbbVie or having stock or other ownership interests in AbbVie.

Source: Allan JN et al. Outcomes in patients with high-risk features after fixed-duration ibrutinib plus venetoclax: Phase II CAPTIVATE study in first-line chronic lymphocytic leukemia. Clin Cancer Res. 2023 (Jun 7). doi: 10.1158/1078-0432.CCR-22-2779

Key clinical point: First-line ibrutinib+venetoclax led to high response and survival rates in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) regardless of high-risk genomic features generally associated with poor outcomes.

Major finding: Overall response and 36-month overall survival rates were >95% regardless of high-risk features. Patients with and without high-risk features had similar complete response (61% [95% CI 53%-70%] and 53% [95% CI 41%-65%], respectively) and 36-month progression-free survival (88% [95% CI 81%-93%] and 92% [95% CI 82%-97%], respectively) rates.

Study details: This post hoc analysis of the CAPTIVATE trial analyzed the pooled data of 195 patients with previously untreated CLL/SLL and known status of high-risk features [del(17p), TP53 mutation, and unmutated immunoglobulin heavy chain] treated with fixed-duration ibrutinib+venetoclax, of which 129 had ≥1 high-risk feature.

Disclosures: This study was funded by Pharmacyclics LLC, an AbbVie Company. Some authors declared receiving grants, personal fees, or other support from Pharmacyclics, AbbVie, or others. Two authors declared being employees of Pharmacyclics or AbbVie or having stock or other ownership interests in AbbVie.

Source: Allan JN et al. Outcomes in patients with high-risk features after fixed-duration ibrutinib plus venetoclax: Phase II CAPTIVATE study in first-line chronic lymphocytic leukemia. Clin Cancer Res. 2023 (Jun 7). doi: 10.1158/1078-0432.CCR-22-2779

Key clinical point: First-line ibrutinib+venetoclax led to high response and survival rates in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) regardless of high-risk genomic features generally associated with poor outcomes.

Major finding: Overall response and 36-month overall survival rates were >95% regardless of high-risk features. Patients with and without high-risk features had similar complete response (61% [95% CI 53%-70%] and 53% [95% CI 41%-65%], respectively) and 36-month progression-free survival (88% [95% CI 81%-93%] and 92% [95% CI 82%-97%], respectively) rates.

Study details: This post hoc analysis of the CAPTIVATE trial analyzed the pooled data of 195 patients with previously untreated CLL/SLL and known status of high-risk features [del(17p), TP53 mutation, and unmutated immunoglobulin heavy chain] treated with fixed-duration ibrutinib+venetoclax, of which 129 had ≥1 high-risk feature.

Disclosures: This study was funded by Pharmacyclics LLC, an AbbVie Company. Some authors declared receiving grants, personal fees, or other support from Pharmacyclics, AbbVie, or others. Two authors declared being employees of Pharmacyclics or AbbVie or having stock or other ownership interests in AbbVie.

Source: Allan JN et al. Outcomes in patients with high-risk features after fixed-duration ibrutinib plus venetoclax: Phase II CAPTIVATE study in first-line chronic lymphocytic leukemia. Clin Cancer Res. 2023 (Jun 7). doi: 10.1158/1078-0432.CCR-22-2779

Key clinical point: The preexistence of depression, anxiety, or both is associated with shorter survival in older patients with diffuse large B-cell lymphoma (DLBCL).

Major finding: At a median follow-up of 2.0 years, patients with depression, anxiety, or both vs without any mental disorder had significantly lower 5-year overall survival rates (27.0% vs 37.4%; hazard ratio [HR] 1.37; 95% CI 1.29-1.44), with those with preexisting depression vs without any mental disorder having the worst rate (23.4% vs 38.0%; HR 1.37; P < .0001).

Study details: This retrospective cohort study analyzed the data of 13,244 patients age ≥ 67 years with DLBCL from the Surveillance, Epidemiology, and End Results-Medicare (SEER) registry, of which 2094 had depression, anxiety, or both at the time of their DLBCL diagnosis.

Disclosures: This study was funded by the American Society of Hematology and others. Some authors declared participating on Data Safety Monitoring or Advisory Boards or receiving financial support, royalties or licenses, or payments or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from various organizations.

Source: Kuczmarski TM et al. Mental health disorders and survival among older patients with diffuse large B-cell lymphoma in the USA: A population-based study. Lancet Haematol. 2023 (Jun 1). doi: 10.1016/S2352-3026(23)00094-7

Key clinical point: The preexistence of depression, anxiety, or both is associated with shorter survival in older patients with diffuse large B-cell lymphoma (DLBCL).

Major finding: At a median follow-up of 2.0 years, patients with depression, anxiety, or both vs without any mental disorder had significantly lower 5-year overall survival rates (27.0% vs 37.4%; hazard ratio [HR] 1.37; 95% CI 1.29-1.44), with those with preexisting depression vs without any mental disorder having the worst rate (23.4% vs 38.0%; HR 1.37; P < .0001).

Study details: This retrospective cohort study analyzed the data of 13,244 patients age ≥ 67 years with DLBCL from the Surveillance, Epidemiology, and End Results-Medicare (SEER) registry, of which 2094 had depression, anxiety, or both at the time of their DLBCL diagnosis.

Disclosures: This study was funded by the American Society of Hematology and others. Some authors declared participating on Data Safety Monitoring or Advisory Boards or receiving financial support, royalties or licenses, or payments or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from various organizations.

Source: Kuczmarski TM et al. Mental health disorders and survival among older patients with diffuse large B-cell lymphoma in the USA: A population-based study. Lancet Haematol. 2023 (Jun 1). doi: 10.1016/S2352-3026(23)00094-7

Key clinical point: The preexistence of depression, anxiety, or both is associated with shorter survival in older patients with diffuse large B-cell lymphoma (DLBCL).

Major finding: At a median follow-up of 2.0 years, patients with depression, anxiety, or both vs without any mental disorder had significantly lower 5-year overall survival rates (27.0% vs 37.4%; hazard ratio [HR] 1.37; 95% CI 1.29-1.44), with those with preexisting depression vs without any mental disorder having the worst rate (23.4% vs 38.0%; HR 1.37; P < .0001).

Study details: This retrospective cohort study analyzed the data of 13,244 patients age ≥ 67 years with DLBCL from the Surveillance, Epidemiology, and End Results-Medicare (SEER) registry, of which 2094 had depression, anxiety, or both at the time of their DLBCL diagnosis.

Disclosures: This study was funded by the American Society of Hematology and others. Some authors declared participating on Data Safety Monitoring or Advisory Boards or receiving financial support, royalties or licenses, or payments or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from various organizations.

Source: Kuczmarski TM et al. Mental health disorders and survival among older patients with diffuse large B-cell lymphoma in the USA: A population-based study. Lancet Haematol. 2023 (Jun 1). doi: 10.1016/S2352-3026(23)00094-7

Key clinical point: Compared with the current standard-of-care chemoimmunotherapy, second-line axicabtagene ciloleucel (axi-cel) significantly prolongs the overall survival of patients with early relapsed or refractory large B-cell lymphoma (LBCL).

Major finding: At a median follow-up of 47.2 months, patients receiving axi-cel vs standard care had a significantly longer median overall survival (not reached vs 31.1 months; hazard ratio 0.73; P = .03) and an absolute improvement in overall survival (8.6 percentage points at 4 years). No new treatment-related deaths were reported since the primary event-free survival analysis.

Study details: This primary overall survival analysis of the phase 3 ZUMA-7 trial included 359 adults with LBCL (refractory to or relapsed after first-line treatment) who were randomly assigned to receive axi-cel (n = 180) or standard care (n = 179).

Disclosures: This study was funded by Kite Pharma. Some authors, including the lead author, declared serving as advisory board members, consultants, or speakers for; receiving research support, speaker fees, travel expenses, or honoraria from; or owning stock or stock options in various sources, including Kite.

Source: Westin JR et al. Survival with axicabtagene ciloleucel in large B-cell lymphoma. N Engl J Med. 2023 (Jun 5). doi: 10.1056/NEJMoa2301665

Key clinical point: Compared with the current standard-of-care chemoimmunotherapy, second-line axicabtagene ciloleucel (axi-cel) significantly prolongs the overall survival of patients with early relapsed or refractory large B-cell lymphoma (LBCL).

Major finding: At a median follow-up of 47.2 months, patients receiving axi-cel vs standard care had a significantly longer median overall survival (not reached vs 31.1 months; hazard ratio 0.73; P = .03) and an absolute improvement in overall survival (8.6 percentage points at 4 years). No new treatment-related deaths were reported since the primary event-free survival analysis.

Study details: This primary overall survival analysis of the phase 3 ZUMA-7 trial included 359 adults with LBCL (refractory to or relapsed after first-line treatment) who were randomly assigned to receive axi-cel (n = 180) or standard care (n = 179).

Disclosures: This study was funded by Kite Pharma. Some authors, including the lead author, declared serving as advisory board members, consultants, or speakers for; receiving research support, speaker fees, travel expenses, or honoraria from; or owning stock or stock options in various sources, including Kite.

Source: Westin JR et al. Survival with axicabtagene ciloleucel in large B-cell lymphoma. N Engl J Med. 2023 (Jun 5). doi: 10.1056/NEJMoa2301665

Key clinical point: Compared with the current standard-of-care chemoimmunotherapy, second-line axicabtagene ciloleucel (axi-cel) significantly prolongs the overall survival of patients with early relapsed or refractory large B-cell lymphoma (LBCL).

Major finding: At a median follow-up of 47.2 months, patients receiving axi-cel vs standard care had a significantly longer median overall survival (not reached vs 31.1 months; hazard ratio 0.73; P = .03) and an absolute improvement in overall survival (8.6 percentage points at 4 years). No new treatment-related deaths were reported since the primary event-free survival analysis.

Study details: This primary overall survival analysis of the phase 3 ZUMA-7 trial included 359 adults with LBCL (refractory to or relapsed after first-line treatment) who were randomly assigned to receive axi-cel (n = 180) or standard care (n = 179).

Disclosures: This study was funded by Kite Pharma. Some authors, including the lead author, declared serving as advisory board members, consultants, or speakers for; receiving research support, speaker fees, travel expenses, or honoraria from; or owning stock or stock options in various sources, including Kite.

Source: Westin JR et al. Survival with axicabtagene ciloleucel in large B-cell lymphoma. N Engl J Med. 2023 (Jun 5). doi: 10.1056/NEJMoa2301665

Key clinical point: Pirtobrutinib demonstrated durable efficacy and a favorable safety profile in patients with covalent Bruton tyrosine kinase inhibitor (cBTKi) pretreated relapsed or refractory mantle cell lymphoma (MCL).

Major finding: The overall response rate was 57.8% (95% CI 46.9%-68.1%), with the complete response rate being 20.0%. At a median follow-up of 12 months, the median duration of response was 21.6 (95% CI 7.5-not reached) months. Grade ≥3 treatment-related adverse events were not frequent, with neutropenia (8.5%) being the most common.

Study details: This multicenter phase 1/2 BRUIN trial included 90 cBTKi pretreated patients with relapsed or refractory MCL in the primary efficacy cohort who received 25-300 mg and 200 mg pirtobrutinib once daily orally in the phases 1 and 2 of the trial, respectively.

Disclosures: This study was sponsored by Loxo Oncology Inc., a wholly owned subsidiary of Eli Lilly and Company. Some authors reported ties with Eli Lilly and others. Seven authors declared being employees of or stockholders in Eli Lilly.

Source: Wang ML et al. Pirtobrutinib in covalent BTK-inhibitor pre-treated mantle cell lymphoma. J Clin Oncol. 2023 (May 16). doi: 10.1200/JCO.23.00562

Key clinical point: Pirtobrutinib demonstrated durable efficacy and a favorable safety profile in patients with covalent Bruton tyrosine kinase inhibitor (cBTKi) pretreated relapsed or refractory mantle cell lymphoma (MCL).

Major finding: The overall response rate was 57.8% (95% CI 46.9%-68.1%), with the complete response rate being 20.0%. At a median follow-up of 12 months, the median duration of response was 21.6 (95% CI 7.5-not reached) months. Grade ≥3 treatment-related adverse events were not frequent, with neutropenia (8.5%) being the most common.

Study details: This multicenter phase 1/2 BRUIN trial included 90 cBTKi pretreated patients with relapsed or refractory MCL in the primary efficacy cohort who received 25-300 mg and 200 mg pirtobrutinib once daily orally in the phases 1 and 2 of the trial, respectively.

Disclosures: This study was sponsored by Loxo Oncology Inc., a wholly owned subsidiary of Eli Lilly and Company. Some authors reported ties with Eli Lilly and others. Seven authors declared being employees of or stockholders in Eli Lilly.

Source: Wang ML et al. Pirtobrutinib in covalent BTK-inhibitor pre-treated mantle cell lymphoma. J Clin Oncol. 2023 (May 16). doi: 10.1200/JCO.23.00562

Key clinical point: Pirtobrutinib demonstrated durable efficacy and a favorable safety profile in patients with covalent Bruton tyrosine kinase inhibitor (cBTKi) pretreated relapsed or refractory mantle cell lymphoma (MCL).

Major finding: The overall response rate was 57.8% (95% CI 46.9%-68.1%), with the complete response rate being 20.0%. At a median follow-up of 12 months, the median duration of response was 21.6 (95% CI 7.5-not reached) months. Grade ≥3 treatment-related adverse events were not frequent, with neutropenia (8.5%) being the most common.

Study details: This multicenter phase 1/2 BRUIN trial included 90 cBTKi pretreated patients with relapsed or refractory MCL in the primary efficacy cohort who received 25-300 mg and 200 mg pirtobrutinib once daily orally in the phases 1 and 2 of the trial, respectively.

Disclosures: This study was sponsored by Loxo Oncology Inc., a wholly owned subsidiary of Eli Lilly and Company. Some authors reported ties with Eli Lilly and others. Seven authors declared being employees of or stockholders in Eli Lilly.

Source: Wang ML et al. Pirtobrutinib in covalent BTK-inhibitor pre-treated mantle cell lymphoma. J Clin Oncol. 2023 (May 16). doi: 10.1200/JCO.23.00562

Patients with chronic lymphocytic leukemia (CLL) – even those who have multiple comorbidities – experience long-term progression-free survival (PFS) benefits with 1 year of venetoclax plus obinutuzumab versus a chemotherapy-based regimen, a 6-year follow-up analysis from CLL14 showed. The research was presented June 9 at the annual meeting of the European Hematology Association.

Initial results from the trial were shown at the EHA 2019 annual meeting and reported at the time by this news organization.

They revealed that, among more than 430 CLL patients with a median age of over 70 years and multiple comorbidities, the combination of venetoclax, a B-cell lymphoma 2 protein blocker, plus obinutuzumab, an anti-CD20 monoclonal antibody, was associated with a 65% improvement in PFS, compared with chlorambucil, a chemotherapy agent, plus obinutuzumab.

On the strength of these findings, the venetoclax-obinutuzumab combination received Food and Drug Administration approval for previously untreated CLL and small lymphocytic lymphoma in March 2019.

The latest analysis, presented by Othman Al-Sawaf, MD, University Hospital of Cologne (Germany), showed that despite having just 12 cycles of treatment, patients treated with venetoclax-obinutuzumab continued to experience a significant PFS benefit over those given the chemotherapy-based regimen, including in high-risk patients, after more than 6 years of follow-up.

Dr. Al-Sawaf noted that more than 50% of patients given the experimental combination remained without a PFS event at the latest follow-up, and that over 60% had not required a second treatment, equating to a 66% reduction in the likelihood of needing a second treatment versus chlorambucil-obinutuzumab.

Dr. Al-Sawaf said at a press conference that, “clinically, the standard of care for any CLL if it is asymptomatic” is watch and wait, which is “true in the frontline setting, but also in the relapse setting.”

Therefore, these patients “do not need to initiate the next line of treatment, and that’s why time to next treatment is so interesting.”

He added that there also were no new safety signals, with adverse event rates dropping markedly once treatment was over, although there was a suggestion of an increase in second malignancies with venetoclax-obinutuzumab.

“We’ve seen, in many studies now that use fixed-duration approaches, that there is virtually no posttreatment toxicity once patients are able to get off treatment,” Dr. Al-Sawaf said, adding: “This really highlights the benefit” of stopping treatment, “which is a clear advantage compared to having any kind of continuous treatment.”

Approached for comment, William G. Wierda, MD, PhD, professor, department of leukemia, division of cancer medicine, University of Texas MD Anderson Cancer Center, Houston, emphasized the value of the 6-year follow-up of the study, adding that these are “very impressive data.”

He told this news organization that, in terms of the ongoing PFS improvement, “we wouldn’t expect anything otherwise” with venetoclax-obinutuzumab when compared with the chemotherapy-based regimen, but that the trend for an improvement in overall survival is of particular interest.

This “is a notable feature of the update,” Dr. Wierda said, and “we will continue to watch the long-term overall survival curves with a longer follow-up,” especially as the separation of the curves between the two regimens is “more prominent” than in previous analyses of CLL14.

He also pointed to the low incidence of grade ≥ 3 adverse events in patients who are in remission, which “support the use of fixed-duration chemo-free” treatments, and the longer follow-up now allowing the contribution of high-risk features to outcomes to be teased out in multivariate analysis.

“The data that we’re looking for in the next update of this is some indication about improved outcomes between patients with a mutated and unmutated immunoglobulin heavy chain gene [IgHV], in regard to undetectable MRD [minimal residual disease] status,” Dr. Wierda said.

“We know that mutational status correlates with progression free survival,” he explained. “What we would like to see moving forward is how that is associated with undetectable MRD status at the end of treatment.”

Dr. Wierda said that the next hotly anticipated trial in the field is CLL17, which is comparing ibrutinib monotherapy to fixed-duration venetoclax-obinutuzumab to fixed-duration ibrutinib-venetoclax in patients with previously untreated CLL.

“That’s the next question: Is there any advantage of a BTK [Bruton’s tyrosine kinase] inhibitor with venetoclax over venetoclax plus the CD20 antibody?”

Dr. Al-Sawaf, in presenting the latest analysis, reminded the audience that CLL14 was a randomized phase 3 study focusing on patients with previously untreated CLL and coexisting conditions who were randomized to either venetoclax-obinutuzumab for six cycles, followed by six cycles of venetoclax, or chlorambucil-obinutuzumab for six cycles, followed by chlorambucil for six cycles.

The patients, who were enrolled between 2015 and 2016, were required to have a Cumulative Illness Rating Scale (CIRS) score > 6 and/or creatinine clearance < 70 mL/min, which Dr. Al-Sawaf explained serves as “indicator of the unfitness of the patients.”

A total of 432 patients took part in the study. The median age across the two treatment groups was 71-72 years, and the median total CIRS score was 8-9. The majority of patients (79%-80%) had Binet stage B or C CLL. An intermediate tumor lysis syndrome risk was identified in 64%-68%.

“We also had a fair share of patients with high-risk disease,” Dr. Al-Sawaf noted, with approximately 60% having an unmutated IGHV status, and 12% having a TP53 mutation, both of which are associated with a poorer prognosis.

He added that the “aim of these long-term observations that we try to do every year is not so much to do the comparisons to chlorambucil-obinutuzumab, which we appreciate is not necessarily a standard of care anymore,” but rather to understand the safety and effectiveness of venetoclax-obinutuzumab “in the long run, given that all patients are off treatment.”

Beginning with the safety data, Dr. Al-Sawaf showed that rates of grade ≥ 3 adverse events plummeted after the treatment period, with rates of neutropenia falling from 51.9% with venetoclax-obinutuzumab and 47.2% with chlorambucil-obinutuzumab during treatment to 3.8% and 1.9%, respectively, post treatment.

Similarly, rates of thrombocytopenia decreased from 14.2% on treatment to 0.5% off treatment in patients given venetoclax-obinutuzumab, and from 15.0% to 0.0% in the chlorambucil-obinutuzumab group.

One note of caution was sounded over the proportion of patients with at least one second primary malignancy following treatment, which was numerically higher with venetoclax-obinutuzumab, at 14.2% versus 8.4% with the chemotherapy-based regimen.

“But this is a rather a heterogeneous pattern of solid organ tumors and melanoma,” Dr. Al-Sawaf said, referring to the additional malignancies in the venetoclax-obinutuzumab arm. These included lung cancer, prostate cancer and breast cancer.

He said, however, there was no “specific pattern that we can really pinpoint ... and, importantly, the difference is not statistically significant.”

Turning to the efficacy outcomes, Dr. Al-Sawaf showed that, after median follow-up of 76.4 months, the separation in PFS between the two treatment arms continued, with the median PFS 76.2 months with venetoclax-obinutuzumab versus 36.4 months with chlorambucil-obinutuzumab, at a hazard ratio 0.40 (P < .0001).

The 6-year PFS rate in patients treated with venetoclax-obinutuzumab was 53.1% versus 21.7% with the chemotherapy-based regimen. Looking at the high-risk groups, Dr. Al-Sawaf reported that there was a similar pattern of benefit with venetoclax-obinutuzumab.

Among patients with a TP53 mutation, the median PFS was 51.9 months with the combination versus 20.8 months in those given chlorambucil-obinutuzumab, while the corresponding durations in patients with unmutated IGHV were 64.8 months and 26.9 months, respectively.

Multivariate analysis demonstrated that IGHV status was an independent predictor of PFS in patients treated with venetoclax-obinutuzumab, as was the presence of a TP53 mutation, and lymph node size ≥ 5 cm.

There was no significant difference in overall survival between the two treatment groups, although there was a numerical difference in 6-year overall survival rates, at 78.7% with the experimental combination versus 69.2% with chlorambucil-obinutuzumab.

Patients with a minimal residual disease (MRD) count ≥ 10-4 had a shorter overall survival than did those with MRD < 10-4.

“We are currently working up to understand which group of patients experiences these tremendous long term remissions,” Dr. Al-Sawaf said, “and we will keep you posted on this.”

He also showed that the time to next treatment (TTNT), defined as time to death or next anti-leukemic treatment, was significantly longer with venetoclax-obinutuzumab, with the median not reached before the current data lock versus 52.9 months with the chemotherapy-based regimen.

This equated to a hazard ratio in favor of the experimental combination of 0.44 (P < .0001), and a 6-year TTNT rate of 65.2% versus 37.1% for chlorambucil-obinutuzumab.

That second treatment was a Bruton’s tyrosine kinase inhibitor in 59.0% of cases in the venetoclax-obinutuzumab arm and 53.4% in the chlorambucil-obinutuzumab group.

Dr. Al-Sawaf noted, however, that 23.1% and 30.1%, respectively, of patients were given a chemotherapy or chemo-immunotherapy regimen, “which we nowadays would not necessarily consider a standard of care.”

“This ultimately reflects, as in many global clinical studies, the disparities that we still have across the world in terms of access to state-of-the-art therapies.”

The study was sponsored by Hoffmann–La Roche, and conducted in collaboration with AbbVie, and the German CLL Study Group. Dr. Al-Sawaf disclosed relationships with AbbVie, Adaptive, Ascentage, AstraZeneca, BeiGene, Gilead, Janssen, Lilly, and Roche.

Patients with chronic lymphocytic leukemia (CLL) – even those who have multiple comorbidities – experience long-term progression-free survival (PFS) benefits with 1 year of venetoclax plus obinutuzumab versus a chemotherapy-based regimen, a 6-year follow-up analysis from CLL14 showed. The research was presented June 9 at the annual meeting of the European Hematology Association.

Initial results from the trial were shown at the EHA 2019 annual meeting and reported at the time by this news organization.

They revealed that, among more than 430 CLL patients with a median age of over 70 years and multiple comorbidities, the combination of venetoclax, a B-cell lymphoma 2 protein blocker, plus obinutuzumab, an anti-CD20 monoclonal antibody, was associated with a 65% improvement in PFS, compared with chlorambucil, a chemotherapy agent, plus obinutuzumab.

On the strength of these findings, the venetoclax-obinutuzumab combination received Food and Drug Administration approval for previously untreated CLL and small lymphocytic lymphoma in March 2019.

The latest analysis, presented by Othman Al-Sawaf, MD, University Hospital of Cologne (Germany), showed that despite having just 12 cycles of treatment, patients treated with venetoclax-obinutuzumab continued to experience a significant PFS benefit over those given the chemotherapy-based regimen, including in high-risk patients, after more than 6 years of follow-up.

Dr. Al-Sawaf noted that more than 50% of patients given the experimental combination remained without a PFS event at the latest follow-up, and that over 60% had not required a second treatment, equating to a 66% reduction in the likelihood of needing a second treatment versus chlorambucil-obinutuzumab.

Dr. Al-Sawaf said at a press conference that, “clinically, the standard of care for any CLL if it is asymptomatic” is watch and wait, which is “true in the frontline setting, but also in the relapse setting.”

Therefore, these patients “do not need to initiate the next line of treatment, and that’s why time to next treatment is so interesting.”

He added that there also were no new safety signals, with adverse event rates dropping markedly once treatment was over, although there was a suggestion of an increase in second malignancies with venetoclax-obinutuzumab.

“We’ve seen, in many studies now that use fixed-duration approaches, that there is virtually no posttreatment toxicity once patients are able to get off treatment,” Dr. Al-Sawaf said, adding: “This really highlights the benefit” of stopping treatment, “which is a clear advantage compared to having any kind of continuous treatment.”

Approached for comment, William G. Wierda, MD, PhD, professor, department of leukemia, division of cancer medicine, University of Texas MD Anderson Cancer Center, Houston, emphasized the value of the 6-year follow-up of the study, adding that these are “very impressive data.”

He told this news organization that, in terms of the ongoing PFS improvement, “we wouldn’t expect anything otherwise” with venetoclax-obinutuzumab when compared with the chemotherapy-based regimen, but that the trend for an improvement in overall survival is of particular interest.

This “is a notable feature of the update,” Dr. Wierda said, and “we will continue to watch the long-term overall survival curves with a longer follow-up,” especially as the separation of the curves between the two regimens is “more prominent” than in previous analyses of CLL14.

He also pointed to the low incidence of grade ≥ 3 adverse events in patients who are in remission, which “support the use of fixed-duration chemo-free” treatments, and the longer follow-up now allowing the contribution of high-risk features to outcomes to be teased out in multivariate analysis.

“The data that we’re looking for in the next update of this is some indication about improved outcomes between patients with a mutated and unmutated immunoglobulin heavy chain gene [IgHV], in regard to undetectable MRD [minimal residual disease] status,” Dr. Wierda said.

“We know that mutational status correlates with progression free survival,” he explained. “What we would like to see moving forward is how that is associated with undetectable MRD status at the end of treatment.”

Dr. Wierda said that the next hotly anticipated trial in the field is CLL17, which is comparing ibrutinib monotherapy to fixed-duration venetoclax-obinutuzumab to fixed-duration ibrutinib-venetoclax in patients with previously untreated CLL.

“That’s the next question: Is there any advantage of a BTK [Bruton’s tyrosine kinase] inhibitor with venetoclax over venetoclax plus the CD20 antibody?”

Dr. Al-Sawaf, in presenting the latest analysis, reminded the audience that CLL14 was a randomized phase 3 study focusing on patients with previously untreated CLL and coexisting conditions who were randomized to either venetoclax-obinutuzumab for six cycles, followed by six cycles of venetoclax, or chlorambucil-obinutuzumab for six cycles, followed by chlorambucil for six cycles.

The patients, who were enrolled between 2015 and 2016, were required to have a Cumulative Illness Rating Scale (CIRS) score > 6 and/or creatinine clearance < 70 mL/min, which Dr. Al-Sawaf explained serves as “indicator of the unfitness of the patients.”

A total of 432 patients took part in the study. The median age across the two treatment groups was 71-72 years, and the median total CIRS score was 8-9. The majority of patients (79%-80%) had Binet stage B or C CLL. An intermediate tumor lysis syndrome risk was identified in 64%-68%.

“We also had a fair share of patients with high-risk disease,” Dr. Al-Sawaf noted, with approximately 60% having an unmutated IGHV status, and 12% having a TP53 mutation, both of which are associated with a poorer prognosis.

He added that the “aim of these long-term observations that we try to do every year is not so much to do the comparisons to chlorambucil-obinutuzumab, which we appreciate is not necessarily a standard of care anymore,” but rather to understand the safety and effectiveness of venetoclax-obinutuzumab “in the long run, given that all patients are off treatment.”

Beginning with the safety data, Dr. Al-Sawaf showed that rates of grade ≥ 3 adverse events plummeted after the treatment period, with rates of neutropenia falling from 51.9% with venetoclax-obinutuzumab and 47.2% with chlorambucil-obinutuzumab during treatment to 3.8% and 1.9%, respectively, post treatment.

Similarly, rates of thrombocytopenia decreased from 14.2% on treatment to 0.5% off treatment in patients given venetoclax-obinutuzumab, and from 15.0% to 0.0% in the chlorambucil-obinutuzumab group.

One note of caution was sounded over the proportion of patients with at least one second primary malignancy following treatment, which was numerically higher with venetoclax-obinutuzumab, at 14.2% versus 8.4% with the chemotherapy-based regimen.

“But this is a rather a heterogeneous pattern of solid organ tumors and melanoma,” Dr. Al-Sawaf said, referring to the additional malignancies in the venetoclax-obinutuzumab arm. These included lung cancer, prostate cancer and breast cancer.

He said, however, there was no “specific pattern that we can really pinpoint ... and, importantly, the difference is not statistically significant.”

Turning to the efficacy outcomes, Dr. Al-Sawaf showed that, after median follow-up of 76.4 months, the separation in PFS between the two treatment arms continued, with the median PFS 76.2 months with venetoclax-obinutuzumab versus 36.4 months with chlorambucil-obinutuzumab, at a hazard ratio 0.40 (P < .0001).

The 6-year PFS rate in patients treated with venetoclax-obinutuzumab was 53.1% versus 21.7% with the chemotherapy-based regimen. Looking at the high-risk groups, Dr. Al-Sawaf reported that there was a similar pattern of benefit with venetoclax-obinutuzumab.

Among patients with a TP53 mutation, the median PFS was 51.9 months with the combination versus 20.8 months in those given chlorambucil-obinutuzumab, while the corresponding durations in patients with unmutated IGHV were 64.8 months and 26.9 months, respectively.

Multivariate analysis demonstrated that IGHV status was an independent predictor of PFS in patients treated with venetoclax-obinutuzumab, as was the presence of a TP53 mutation, and lymph node size ≥ 5 cm.

There was no significant difference in overall survival between the two treatment groups, although there was a numerical difference in 6-year overall survival rates, at 78.7% with the experimental combination versus 69.2% with chlorambucil-obinutuzumab.

Patients with a minimal residual disease (MRD) count ≥ 10-4 had a shorter overall survival than did those with MRD < 10-4.

“We are currently working up to understand which group of patients experiences these tremendous long term remissions,” Dr. Al-Sawaf said, “and we will keep you posted on this.”

He also showed that the time to next treatment (TTNT), defined as time to death or next anti-leukemic treatment, was significantly longer with venetoclax-obinutuzumab, with the median not reached before the current data lock versus 52.9 months with the chemotherapy-based regimen.

This equated to a hazard ratio in favor of the experimental combination of 0.44 (P < .0001), and a 6-year TTNT rate of 65.2% versus 37.1% for chlorambucil-obinutuzumab.

That second treatment was a Bruton’s tyrosine kinase inhibitor in 59.0% of cases in the venetoclax-obinutuzumab arm and 53.4% in the chlorambucil-obinutuzumab group.

Dr. Al-Sawaf noted, however, that 23.1% and 30.1%, respectively, of patients were given a chemotherapy or chemo-immunotherapy regimen, “which we nowadays would not necessarily consider a standard of care.”

“This ultimately reflects, as in many global clinical studies, the disparities that we still have across the world in terms of access to state-of-the-art therapies.”

The study was sponsored by Hoffmann–La Roche, and conducted in collaboration with AbbVie, and the German CLL Study Group. Dr. Al-Sawaf disclosed relationships with AbbVie, Adaptive, Ascentage, AstraZeneca, BeiGene, Gilead, Janssen, Lilly, and Roche.

Patients with chronic lymphocytic leukemia (CLL) – even those who have multiple comorbidities – experience long-term progression-free survival (PFS) benefits with 1 year of venetoclax plus obinutuzumab versus a chemotherapy-based regimen, a 6-year follow-up analysis from CLL14 showed. The research was presented June 9 at the annual meeting of the European Hematology Association.

Initial results from the trial were shown at the EHA 2019 annual meeting and reported at the time by this news organization.

They revealed that, among more than 430 CLL patients with a median age of over 70 years and multiple comorbidities, the combination of venetoclax, a B-cell lymphoma 2 protein blocker, plus obinutuzumab, an anti-CD20 monoclonal antibody, was associated with a 65% improvement in PFS, compared with chlorambucil, a chemotherapy agent, plus obinutuzumab.

On the strength of these findings, the venetoclax-obinutuzumab combination received Food and Drug Administration approval for previously untreated CLL and small lymphocytic lymphoma in March 2019.

The latest analysis, presented by Othman Al-Sawaf, MD, University Hospital of Cologne (Germany), showed that despite having just 12 cycles of treatment, patients treated with venetoclax-obinutuzumab continued to experience a significant PFS benefit over those given the chemotherapy-based regimen, including in high-risk patients, after more than 6 years of follow-up.

Dr. Al-Sawaf noted that more than 50% of patients given the experimental combination remained without a PFS event at the latest follow-up, and that over 60% had not required a second treatment, equating to a 66% reduction in the likelihood of needing a second treatment versus chlorambucil-obinutuzumab.

Dr. Al-Sawaf said at a press conference that, “clinically, the standard of care for any CLL if it is asymptomatic” is watch and wait, which is “true in the frontline setting, but also in the relapse setting.”

Therefore, these patients “do not need to initiate the next line of treatment, and that’s why time to next treatment is so interesting.”

He added that there also were no new safety signals, with adverse event rates dropping markedly once treatment was over, although there was a suggestion of an increase in second malignancies with venetoclax-obinutuzumab.

“We’ve seen, in many studies now that use fixed-duration approaches, that there is virtually no posttreatment toxicity once patients are able to get off treatment,” Dr. Al-Sawaf said, adding: “This really highlights the benefit” of stopping treatment, “which is a clear advantage compared to having any kind of continuous treatment.”

Approached for comment, William G. Wierda, MD, PhD, professor, department of leukemia, division of cancer medicine, University of Texas MD Anderson Cancer Center, Houston, emphasized the value of the 6-year follow-up of the study, adding that these are “very impressive data.”

He told this news organization that, in terms of the ongoing PFS improvement, “we wouldn’t expect anything otherwise” with venetoclax-obinutuzumab when compared with the chemotherapy-based regimen, but that the trend for an improvement in overall survival is of particular interest.

This “is a notable feature of the update,” Dr. Wierda said, and “we will continue to watch the long-term overall survival curves with a longer follow-up,” especially as the separation of the curves between the two regimens is “more prominent” than in previous analyses of CLL14.

He also pointed to the low incidence of grade ≥ 3 adverse events in patients who are in remission, which “support the use of fixed-duration chemo-free” treatments, and the longer follow-up now allowing the contribution of high-risk features to outcomes to be teased out in multivariate analysis.

“The data that we’re looking for in the next update of this is some indication about improved outcomes between patients with a mutated and unmutated immunoglobulin heavy chain gene [IgHV], in regard to undetectable MRD [minimal residual disease] status,” Dr. Wierda said.

“We know that mutational status correlates with progression free survival,” he explained. “What we would like to see moving forward is how that is associated with undetectable MRD status at the end of treatment.”

Dr. Wierda said that the next hotly anticipated trial in the field is CLL17, which is comparing ibrutinib monotherapy to fixed-duration venetoclax-obinutuzumab to fixed-duration ibrutinib-venetoclax in patients with previously untreated CLL.

“That’s the next question: Is there any advantage of a BTK [Bruton’s tyrosine kinase] inhibitor with venetoclax over venetoclax plus the CD20 antibody?”

Dr. Al-Sawaf, in presenting the latest analysis, reminded the audience that CLL14 was a randomized phase 3 study focusing on patients with previously untreated CLL and coexisting conditions who were randomized to either venetoclax-obinutuzumab for six cycles, followed by six cycles of venetoclax, or chlorambucil-obinutuzumab for six cycles, followed by chlorambucil for six cycles.

The patients, who were enrolled between 2015 and 2016, were required to have a Cumulative Illness Rating Scale (CIRS) score > 6 and/or creatinine clearance < 70 mL/min, which Dr. Al-Sawaf explained serves as “indicator of the unfitness of the patients.”

A total of 432 patients took part in the study. The median age across the two treatment groups was 71-72 years, and the median total CIRS score was 8-9. The majority of patients (79%-80%) had Binet stage B or C CLL. An intermediate tumor lysis syndrome risk was identified in 64%-68%.

“We also had a fair share of patients with high-risk disease,” Dr. Al-Sawaf noted, with approximately 60% having an unmutated IGHV status, and 12% having a TP53 mutation, both of which are associated with a poorer prognosis.

He added that the “aim of these long-term observations that we try to do every year is not so much to do the comparisons to chlorambucil-obinutuzumab, which we appreciate is not necessarily a standard of care anymore,” but rather to understand the safety and effectiveness of venetoclax-obinutuzumab “in the long run, given that all patients are off treatment.”

Beginning with the safety data, Dr. Al-Sawaf showed that rates of grade ≥ 3 adverse events plummeted after the treatment period, with rates of neutropenia falling from 51.9% with venetoclax-obinutuzumab and 47.2% with chlorambucil-obinutuzumab during treatment to 3.8% and 1.9%, respectively, post treatment.

Similarly, rates of thrombocytopenia decreased from 14.2% on treatment to 0.5% off treatment in patients given venetoclax-obinutuzumab, and from 15.0% to 0.0% in the chlorambucil-obinutuzumab group.

One note of caution was sounded over the proportion of patients with at least one second primary malignancy following treatment, which was numerically higher with venetoclax-obinutuzumab, at 14.2% versus 8.4% with the chemotherapy-based regimen.

“But this is a rather a heterogeneous pattern of solid organ tumors and melanoma,” Dr. Al-Sawaf said, referring to the additional malignancies in the venetoclax-obinutuzumab arm. These included lung cancer, prostate cancer and breast cancer.

He said, however, there was no “specific pattern that we can really pinpoint ... and, importantly, the difference is not statistically significant.”

Turning to the efficacy outcomes, Dr. Al-Sawaf showed that, after median follow-up of 76.4 months, the separation in PFS between the two treatment arms continued, with the median PFS 76.2 months with venetoclax-obinutuzumab versus 36.4 months with chlorambucil-obinutuzumab, at a hazard ratio 0.40 (P < .0001).

The 6-year PFS rate in patients treated with venetoclax-obinutuzumab was 53.1% versus 21.7% with the chemotherapy-based regimen. Looking at the high-risk groups, Dr. Al-Sawaf reported that there was a similar pattern of benefit with venetoclax-obinutuzumab.

Among patients with a TP53 mutation, the median PFS was 51.9 months with the combination versus 20.8 months in those given chlorambucil-obinutuzumab, while the corresponding durations in patients with unmutated IGHV were 64.8 months and 26.9 months, respectively.

Multivariate analysis demonstrated that IGHV status was an independent predictor of PFS in patients treated with venetoclax-obinutuzumab, as was the presence of a TP53 mutation, and lymph node size ≥ 5 cm.

There was no significant difference in overall survival between the two treatment groups, although there was a numerical difference in 6-year overall survival rates, at 78.7% with the experimental combination versus 69.2% with chlorambucil-obinutuzumab.

Patients with a minimal residual disease (MRD) count ≥ 10-4 had a shorter overall survival than did those with MRD < 10-4.

“We are currently working up to understand which group of patients experiences these tremendous long term remissions,” Dr. Al-Sawaf said, “and we will keep you posted on this.”

He also showed that the time to next treatment (TTNT), defined as time to death or next anti-leukemic treatment, was significantly longer with venetoclax-obinutuzumab, with the median not reached before the current data lock versus 52.9 months with the chemotherapy-based regimen.

This equated to a hazard ratio in favor of the experimental combination of 0.44 (P < .0001), and a 6-year TTNT rate of 65.2% versus 37.1% for chlorambucil-obinutuzumab.

That second treatment was a Bruton’s tyrosine kinase inhibitor in 59.0% of cases in the venetoclax-obinutuzumab arm and 53.4% in the chlorambucil-obinutuzumab group.

Dr. Al-Sawaf noted, however, that 23.1% and 30.1%, respectively, of patients were given a chemotherapy or chemo-immunotherapy regimen, “which we nowadays would not necessarily consider a standard of care.”

“This ultimately reflects, as in many global clinical studies, the disparities that we still have across the world in terms of access to state-of-the-art therapies.”

The study was sponsored by Hoffmann–La Roche, and conducted in collaboration with AbbVie, and the German CLL Study Group. Dr. Al-Sawaf disclosed relationships with AbbVie, Adaptive, Ascentage, AstraZeneca, BeiGene, Gilead, Janssen, Lilly, and Roche.

The Food and Drug Administration has granted accelerated approval for glofitamab (Columvi) for use in certain types of lymphoma.

The indication is for use in adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified or with LBCL arising from follicular lymphoma who have received two or more lines of systemic therapy.

The product is a T cell–engaging bispecific antibody developed by Genentech, which has a similar product, mosunetuzumab-axgb (Lunsumio), for the treatment of follicular lymphoma. Lunsumio was approved in December 2022.

These drugs could be considered a first choice in the setting of third-line therapy, suggests an expert writing recently in The New England Journal of Medicine.

Nancy Bartlett, MD, from the Siteman Cancer Center, Washington University in St. Louis, is the author of an editorial that accompanied the publication of results with glofitamab in the pivotal trial that led to its approval.

“Bispecific agents will be an excellent option for the 60% of patients in whom second-line CAR [chimeric antigen receptor] T-cell therapy fails,” she wrote in her editorial.

Dr. Bartlett suggests that these agents may be preferred over CAR T cells. “If longer follow-up confirms that the majority of complete remissions with bispecific agents are durable, on the basis of the advantages of availability (including in the community setting) and more favorable immediate and late toxic-effect profiles, bispecific agents could be considered as the initial choice. ... CAR T-cell therapy could be held in reserve for patients who do not have a complete response or who have a relapse after a complete response.”
 

Most common form of non-Hodgkin’s lymphoma

DLBCL is the most common form of non-Hodgkin’s lymphoma in the United States, the company noted in a press release. While many people with DLBCL are responsive to treatment, the majority of those who experience relapse or whose condition is refractory to subsequent treatments have poor outcomes.

“Patients with relapsed or refractory diffuse large B-cell lymphoma may experience rapid progression of their cancer and often urgently need an effective treatment option that can be administered without delay,” commented Krish Patel, MD, director of the lymphoma program at the Swedish Cancer Institute in Seattle, who is an investigator on the clinical trial that led to the product’s approval. He said that the results from trials suggest that glofitamab gives patients “a chance for complete remission with a fixed-duration immunotherapy and that such remissions can potentially be sustained after the end of their treatment.”

The accelerated approval is based on response rate and durability of response results from the phase 1/2 NP30179 study.

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

This trial involved 132 patients with DLBCL who experienced relapse or whose condition was refractory to prior therapies. About one-third of patients (30%) had received prior CAR T-cell therapy. Additionally, for 83% of patients, the condition was refractory to their most recent therapy.

Glofitamab was given to all patients as a fixed course for 8.5 months.

More than half (56%) achieved an overall response, and 43% achieved a complete response. Over two-thirds (68.5%) of those who responded continued to respond for at least 9 months The median duration of response was 1.5 years.

The most common adverse events were cytokine release syndrome (CRS; 70%), which may be serious or life-threatening; musculoskeletal pain (21%); fatigue (20%); and rash (20%). CRS was generally of low grade (52% of patients experienced grade 1 CRS, and 14% experienced grade 2).

Results from the NP30179 trial were published in December 2022.

The complete response rates seen with glofitamab rivals the durable complete response that has been observed with CAR T-cell therapy, Dr. Bartlett noted in the accompanying editorial. “Although these results are promising, it is still too early to estimate the curative potential of glofitamab.”

The Food and Drug Administration has granted accelerated approval for glofitamab (Columvi) for use in certain types of lymphoma.

The indication is for use in adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified or with LBCL arising from follicular lymphoma who have received two or more lines of systemic therapy.

The product is a T cell–engaging bispecific antibody developed by Genentech, which has a similar product, mosunetuzumab-axgb (Lunsumio), for the treatment of follicular lymphoma. Lunsumio was approved in December 2022.

These drugs could be considered a first choice in the setting of third-line therapy, suggests an expert writing recently in The New England Journal of Medicine.

Nancy Bartlett, MD, from the Siteman Cancer Center, Washington University in St. Louis, is the author of an editorial that accompanied the publication of results with glofitamab in the pivotal trial that led to its approval.

“Bispecific agents will be an excellent option for the 60% of patients in whom second-line CAR [chimeric antigen receptor] T-cell therapy fails,” she wrote in her editorial.

Dr. Bartlett suggests that these agents may be preferred over CAR T cells. “If longer follow-up confirms that the majority of complete remissions with bispecific agents are durable, on the basis of the advantages of availability (including in the community setting) and more favorable immediate and late toxic-effect profiles, bispecific agents could be considered as the initial choice. ... CAR T-cell therapy could be held in reserve for patients who do not have a complete response or who have a relapse after a complete response.”
 

Most common form of non-Hodgkin’s lymphoma

DLBCL is the most common form of non-Hodgkin’s lymphoma in the United States, the company noted in a press release. While many people with DLBCL are responsive to treatment, the majority of those who experience relapse or whose condition is refractory to subsequent treatments have poor outcomes.

“Patients with relapsed or refractory diffuse large B-cell lymphoma may experience rapid progression of their cancer and often urgently need an effective treatment option that can be administered without delay,” commented Krish Patel, MD, director of the lymphoma program at the Swedish Cancer Institute in Seattle, who is an investigator on the clinical trial that led to the product’s approval. He said that the results from trials suggest that glofitamab gives patients “a chance for complete remission with a fixed-duration immunotherapy and that such remissions can potentially be sustained after the end of their treatment.”

The accelerated approval is based on response rate and durability of response results from the phase 1/2 NP30179 study.

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

This trial involved 132 patients with DLBCL who experienced relapse or whose condition was refractory to prior therapies. About one-third of patients (30%) had received prior CAR T-cell therapy. Additionally, for 83% of patients, the condition was refractory to their most recent therapy.

Glofitamab was given to all patients as a fixed course for 8.5 months.

More than half (56%) achieved an overall response, and 43% achieved a complete response. Over two-thirds (68.5%) of those who responded continued to respond for at least 9 months The median duration of response was 1.5 years.

The most common adverse events were cytokine release syndrome (CRS; 70%), which may be serious or life-threatening; musculoskeletal pain (21%); fatigue (20%); and rash (20%). CRS was generally of low grade (52% of patients experienced grade 1 CRS, and 14% experienced grade 2).

Results from the NP30179 trial were published in December 2022.

The complete response rates seen with glofitamab rivals the durable complete response that has been observed with CAR T-cell therapy, Dr. Bartlett noted in the accompanying editorial. “Although these results are promising, it is still too early to estimate the curative potential of glofitamab.”

The Food and Drug Administration has granted accelerated approval for glofitamab (Columvi) for use in certain types of lymphoma.

The indication is for use in adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified or with LBCL arising from follicular lymphoma who have received two or more lines of systemic therapy.

The product is a T cell–engaging bispecific antibody developed by Genentech, which has a similar product, mosunetuzumab-axgb (Lunsumio), for the treatment of follicular lymphoma. Lunsumio was approved in December 2022.

These drugs could be considered a first choice in the setting of third-line therapy, suggests an expert writing recently in The New England Journal of Medicine.

Nancy Bartlett, MD, from the Siteman Cancer Center, Washington University in St. Louis, is the author of an editorial that accompanied the publication of results with glofitamab in the pivotal trial that led to its approval.

“Bispecific agents will be an excellent option for the 60% of patients in whom second-line CAR [chimeric antigen receptor] T-cell therapy fails,” she wrote in her editorial.

Dr. Bartlett suggests that these agents may be preferred over CAR T cells. “If longer follow-up confirms that the majority of complete remissions with bispecific agents are durable, on the basis of the advantages of availability (including in the community setting) and more favorable immediate and late toxic-effect profiles, bispecific agents could be considered as the initial choice. ... CAR T-cell therapy could be held in reserve for patients who do not have a complete response or who have a relapse after a complete response.”
 

Most common form of non-Hodgkin’s lymphoma

DLBCL is the most common form of non-Hodgkin’s lymphoma in the United States, the company noted in a press release. While many people with DLBCL are responsive to treatment, the majority of those who experience relapse or whose condition is refractory to subsequent treatments have poor outcomes.

“Patients with relapsed or refractory diffuse large B-cell lymphoma may experience rapid progression of their cancer and often urgently need an effective treatment option that can be administered without delay,” commented Krish Patel, MD, director of the lymphoma program at the Swedish Cancer Institute in Seattle, who is an investigator on the clinical trial that led to the product’s approval. He said that the results from trials suggest that glofitamab gives patients “a chance for complete remission with a fixed-duration immunotherapy and that such remissions can potentially be sustained after the end of their treatment.”

The accelerated approval is based on response rate and durability of response results from the phase 1/2 NP30179 study.

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

This trial involved 132 patients with DLBCL who experienced relapse or whose condition was refractory to prior therapies. About one-third of patients (30%) had received prior CAR T-cell therapy. Additionally, for 83% of patients, the condition was refractory to their most recent therapy.

Glofitamab was given to all patients as a fixed course for 8.5 months.

More than half (56%) achieved an overall response, and 43% achieved a complete response. Over two-thirds (68.5%) of those who responded continued to respond for at least 9 months The median duration of response was 1.5 years.

The most common adverse events were cytokine release syndrome (CRS; 70%), which may be serious or life-threatening; musculoskeletal pain (21%); fatigue (20%); and rash (20%). CRS was generally of low grade (52% of patients experienced grade 1 CRS, and 14% experienced grade 2).

Results from the NP30179 trial were published in December 2022.

The complete response rates seen with glofitamab rivals the durable complete response that has been observed with CAR T-cell therapy, Dr. Bartlett noted in the accompanying editorial. “Although these results are promising, it is still too early to estimate the curative potential of glofitamab.”

At a median follow-up of 47.2 months, axicabtagene ciloleucel (axi-cel, Yescarta) significantly improved overall survival compared with standard second-line treatments in patients with early relapsed or refractory large B-cell lymphoma, according to a phase 3 investigation reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

The anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy was approved for second-line treatment in 2022 based on better event-free survival, but standard second-line treatment – chemoimmunotherapy followed by high-dose chemotherapy and autologous stem-cell transplant in responders – still remains the prevailing approach, explained Jason Westin, MD, director of lymphoma research at MD Anderson Cancer Center, Houston. Dr. Westin, lead investigator, presented the trial, dubbed ZUMA-7, at the ASCO meeting.

The new findings might change that. ZUMA-7 “conclusively demonstrates that trying chemotherapy in the second line and saving cell therapy for the third line is an inferior approach ... ZUMA-7 confirms axi-cel is a second-line standard of care for patients with refractory or early relapsed large B cell lymphoma based on superior overall survival,” said Dr. Westin.

Study discussant Asher A. Chanan-Khan, MD, a CAR-T specialist at the Mayo Clinic in Jacksonville, Fla., agreed.

“This data must alter the current standard of care making CAR-T or axi-cel, based on the data we heard, a preferred second-line treatment ... Moving CAR-T earlier in the treatment paradigm is likely a better choice for our patients,” he said.

The study was published in the New England Journal of Medicine to coincide with the presentations.

Dr. Westin noted that axi-cel is now under investigation in ZUMA-23 for first-line treatment of high-risk large B-cell lymphoma (LBCL).


 

Study details

Zuma-7 randomized 180 LBCL patients to a one-time axi-cel infusion and 179 to standard care. Patients were refractory to first line chemoimmunotherapy or had relapsed within 12 months; just 36% of patients in the standard care group did well enough on treatment to go on to stem-cell transplant.

Median progression-free survival (PFS) was 14.7 months with axi-cel versus 3.7 months with standard care.

Significantly, the better PFS appears to have translated into better overall survival (OS).

At a median of almost 4 years, 82 patients in the axi-cel group had died, compared with 95 patients with standard care who had died. Estimated 4-year OS was 54.6% with axi-cel versus 46% with standard care (HR 0.73, P = .03).

The OS benefit held in high-risk subgroups, including patients over 64 years old, those refractory to first-line treatment, and patients with high-grade disease.

Adverse events were in keeping with labeling. Cytokine release syndrome was more common in the axi-cel arm, including grade 3 or worse CRS in 6% of axi-cel patients versus none on standard care. Grade 3 or worse infections were also more common at 16.5% versus 11.9% with standard care. Over 11% of axi-cel patients developed hypogammaglobulinemia versus 0.6% in the standard care group.

Overall, there were no new serious or fatal adverse events since the initial PFS results were reported in 2022, when eight fatal adverse events were reported with axi-cel versus two with standard care.

The work was funded by axi-cel maker Kite Pharma, a subsidiary of Gilead. Investigators included Kite/Gilead employees and others who reported financial relationships with the companies, including Dr. Westin, a Kite/Gilead researcher and adviser. Dr. Chanan-Khan disclosed ties with Cellectar, Starton Therapeutics, Ascentage Pharma, and others.

At a median follow-up of 47.2 months, axicabtagene ciloleucel (axi-cel, Yescarta) significantly improved overall survival compared with standard second-line treatments in patients with early relapsed or refractory large B-cell lymphoma, according to a phase 3 investigation reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

The anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy was approved for second-line treatment in 2022 based on better event-free survival, but standard second-line treatment – chemoimmunotherapy followed by high-dose chemotherapy and autologous stem-cell transplant in responders – still remains the prevailing approach, explained Jason Westin, MD, director of lymphoma research at MD Anderson Cancer Center, Houston. Dr. Westin, lead investigator, presented the trial, dubbed ZUMA-7, at the ASCO meeting.

The new findings might change that. ZUMA-7 “conclusively demonstrates that trying chemotherapy in the second line and saving cell therapy for the third line is an inferior approach ... ZUMA-7 confirms axi-cel is a second-line standard of care for patients with refractory or early relapsed large B cell lymphoma based on superior overall survival,” said Dr. Westin.

Study discussant Asher A. Chanan-Khan, MD, a CAR-T specialist at the Mayo Clinic in Jacksonville, Fla., agreed.

“This data must alter the current standard of care making CAR-T or axi-cel, based on the data we heard, a preferred second-line treatment ... Moving CAR-T earlier in the treatment paradigm is likely a better choice for our patients,” he said.

The study was published in the New England Journal of Medicine to coincide with the presentations.

Dr. Westin noted that axi-cel is now under investigation in ZUMA-23 for first-line treatment of high-risk large B-cell lymphoma (LBCL).


 

Study details

Zuma-7 randomized 180 LBCL patients to a one-time axi-cel infusion and 179 to standard care. Patients were refractory to first line chemoimmunotherapy or had relapsed within 12 months; just 36% of patients in the standard care group did well enough on treatment to go on to stem-cell transplant.

Median progression-free survival (PFS) was 14.7 months with axi-cel versus 3.7 months with standard care.

Significantly, the better PFS appears to have translated into better overall survival (OS).

At a median of almost 4 years, 82 patients in the axi-cel group had died, compared with 95 patients with standard care who had died. Estimated 4-year OS was 54.6% with axi-cel versus 46% with standard care (HR 0.73, P = .03).

The OS benefit held in high-risk subgroups, including patients over 64 years old, those refractory to first-line treatment, and patients with high-grade disease.

Adverse events were in keeping with labeling. Cytokine release syndrome was more common in the axi-cel arm, including grade 3 or worse CRS in 6% of axi-cel patients versus none on standard care. Grade 3 or worse infections were also more common at 16.5% versus 11.9% with standard care. Over 11% of axi-cel patients developed hypogammaglobulinemia versus 0.6% in the standard care group.

Overall, there were no new serious or fatal adverse events since the initial PFS results were reported in 2022, when eight fatal adverse events were reported with axi-cel versus two with standard care.

The work was funded by axi-cel maker Kite Pharma, a subsidiary of Gilead. Investigators included Kite/Gilead employees and others who reported financial relationships with the companies, including Dr. Westin, a Kite/Gilead researcher and adviser. Dr. Chanan-Khan disclosed ties with Cellectar, Starton Therapeutics, Ascentage Pharma, and others.

At a median follow-up of 47.2 months, axicabtagene ciloleucel (axi-cel, Yescarta) significantly improved overall survival compared with standard second-line treatments in patients with early relapsed or refractory large B-cell lymphoma, according to a phase 3 investigation reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

The anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy was approved for second-line treatment in 2022 based on better event-free survival, but standard second-line treatment – chemoimmunotherapy followed by high-dose chemotherapy and autologous stem-cell transplant in responders – still remains the prevailing approach, explained Jason Westin, MD, director of lymphoma research at MD Anderson Cancer Center, Houston. Dr. Westin, lead investigator, presented the trial, dubbed ZUMA-7, at the ASCO meeting.

The new findings might change that. ZUMA-7 “conclusively demonstrates that trying chemotherapy in the second line and saving cell therapy for the third line is an inferior approach ... ZUMA-7 confirms axi-cel is a second-line standard of care for patients with refractory or early relapsed large B cell lymphoma based on superior overall survival,” said Dr. Westin.

Study discussant Asher A. Chanan-Khan, MD, a CAR-T specialist at the Mayo Clinic in Jacksonville, Fla., agreed.

“This data must alter the current standard of care making CAR-T or axi-cel, based on the data we heard, a preferred second-line treatment ... Moving CAR-T earlier in the treatment paradigm is likely a better choice for our patients,” he said.

The study was published in the New England Journal of Medicine to coincide with the presentations.

Dr. Westin noted that axi-cel is now under investigation in ZUMA-23 for first-line treatment of high-risk large B-cell lymphoma (LBCL).


 

Study details

Zuma-7 randomized 180 LBCL patients to a one-time axi-cel infusion and 179 to standard care. Patients were refractory to first line chemoimmunotherapy or had relapsed within 12 months; just 36% of patients in the standard care group did well enough on treatment to go on to stem-cell transplant.

Median progression-free survival (PFS) was 14.7 months with axi-cel versus 3.7 months with standard care.

Significantly, the better PFS appears to have translated into better overall survival (OS).

At a median of almost 4 years, 82 patients in the axi-cel group had died, compared with 95 patients with standard care who had died. Estimated 4-year OS was 54.6% with axi-cel versus 46% with standard care (HR 0.73, P = .03).

The OS benefit held in high-risk subgroups, including patients over 64 years old, those refractory to first-line treatment, and patients with high-grade disease.

Adverse events were in keeping with labeling. Cytokine release syndrome was more common in the axi-cel arm, including grade 3 or worse CRS in 6% of axi-cel patients versus none on standard care. Grade 3 or worse infections were also more common at 16.5% versus 11.9% with standard care. Over 11% of axi-cel patients developed hypogammaglobulinemia versus 0.6% in the standard care group.

Overall, there were no new serious or fatal adverse events since the initial PFS results were reported in 2022, when eight fatal adverse events were reported with axi-cel versus two with standard care.

The work was funded by axi-cel maker Kite Pharma, a subsidiary of Gilead. Investigators included Kite/Gilead employees and others who reported financial relationships with the companies, including Dr. Westin, a Kite/Gilead researcher and adviser. Dr. Chanan-Khan disclosed ties with Cellectar, Starton Therapeutics, Ascentage Pharma, and others.

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

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

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

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

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

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