Key clinical point: Tumor involvement within the axillary soft tissue extending beyond the positive lymph node (LN+) and extracapsular extension (ECE) should be pathologically evaluated in patients with LN+ breast cancer (BC) as it is a significant predictor of worsened prognostic outcomes for this population.

Major finding: Axillary soft tissue involvement is significantly associated with worsened distant failure (hazard ratio [HR] 1.6; P < .001), locoregional failure (HR 2.3; P < .001), and axillary failure (HR 3.3; P = .003). The delivery of regional lymph node radiation improved the locoregional tumor outcomes in patients with axillary soft tissue involvement, ECE, or both (HR 0.5; P = .03).

Study details: Findings are from a retrospective review including 2162 patients with LN+ invasive BC tumors.

Disclosures: One author declared receiving financial support for this study. Two authors declared being employees of, receiving research funding, or honoraria from, or having other ties with various sources.

Source: Naoum GE, Oladero O, et al. Pathological exploration of the axillary soft tissue microenvironment and its impact on axillary management and breast cancer outcomes. J Clin Oncol. 2023 (Nov 15). doi: 10.1200/JCO.23.01009

Key clinical point: Tumor involvement within the axillary soft tissue extending beyond the positive lymph node (LN+) and extracapsular extension (ECE) should be pathologically evaluated in patients with LN+ breast cancer (BC) as it is a significant predictor of worsened prognostic outcomes for this population.

Major finding: Axillary soft tissue involvement is significantly associated with worsened distant failure (hazard ratio [HR] 1.6; P < .001), locoregional failure (HR 2.3; P < .001), and axillary failure (HR 3.3; P = .003). The delivery of regional lymph node radiation improved the locoregional tumor outcomes in patients with axillary soft tissue involvement, ECE, or both (HR 0.5; P = .03).

Study details: Findings are from a retrospective review including 2162 patients with LN+ invasive BC tumors.

Disclosures: One author declared receiving financial support for this study. Two authors declared being employees of, receiving research funding, or honoraria from, or having other ties with various sources.

Source: Naoum GE, Oladero O, et al. Pathological exploration of the axillary soft tissue microenvironment and its impact on axillary management and breast cancer outcomes. J Clin Oncol. 2023 (Nov 15). doi: 10.1200/JCO.23.01009

Key clinical point: Tumor involvement within the axillary soft tissue extending beyond the positive lymph node (LN+) and extracapsular extension (ECE) should be pathologically evaluated in patients with LN+ breast cancer (BC) as it is a significant predictor of worsened prognostic outcomes for this population.

Major finding: Axillary soft tissue involvement is significantly associated with worsened distant failure (hazard ratio [HR] 1.6; P < .001), locoregional failure (HR 2.3; P < .001), and axillary failure (HR 3.3; P = .003). The delivery of regional lymph node radiation improved the locoregional tumor outcomes in patients with axillary soft tissue involvement, ECE, or both (HR 0.5; P = .03).

Study details: Findings are from a retrospective review including 2162 patients with LN+ invasive BC tumors.

Disclosures: One author declared receiving financial support for this study. Two authors declared being employees of, receiving research funding, or honoraria from, or having other ties with various sources.

Source: Naoum GE, Oladero O, et al. Pathological exploration of the axillary soft tissue microenvironment and its impact on axillary management and breast cancer outcomes. J Clin Oncol. 2023 (Nov 15). doi: 10.1200/JCO.23.01009

Key clinical point: Chemotherapy-related amenorrhea (CRA) was common in premenopausal women with stages I-III breast cancer (BC), particularly in those who were older, experienced hot flashes, or received adjuvant tamoxifen.

Major finding: The majority (57.1%) of premenopausal patients with BC reported having persistent CRA, with the likelihood increasing in those who were age ≥ 35 years (adjusted odds ratio [aOR] 35-39 years: 1.84, 40-44 years: 5.90, ≥45 years: 21.29; all P < .001), experienced hot flashes at diagnosis (aOR 1.83; P = .01), or received adjuvant tamoxifen (aOR 1.97; P < .001).

Study details: This study analyzed the data from the Cancer Toxicities Study and included 1636 premenopausal women with stages I-III BC who were age < 50 years and received chemotherapy but not ovarian function suppressants.

Disclosures: MA Franzoi, M Lambertini, and A Di Meglio received grants or awards for this study. Some authors declared receiving personal fees, speaking fees, grants, or honoraria from or having other ties with various sources.

Source: Kabirian R et al. Chemotherapy-related amenorrhea and quality of life among premenopausal women with breast cancer. JAMA Netw Open. 2023;6(11):e2343910 (Nov 16). doi: 10.1001/jamanetworkopen.2023.43910

Key clinical point: Chemotherapy-related amenorrhea (CRA) was common in premenopausal women with stages I-III breast cancer (BC), particularly in those who were older, experienced hot flashes, or received adjuvant tamoxifen.

Major finding: The majority (57.1%) of premenopausal patients with BC reported having persistent CRA, with the likelihood increasing in those who were age ≥ 35 years (adjusted odds ratio [aOR] 35-39 years: 1.84, 40-44 years: 5.90, ≥45 years: 21.29; all P < .001), experienced hot flashes at diagnosis (aOR 1.83; P = .01), or received adjuvant tamoxifen (aOR 1.97; P < .001).

Study details: This study analyzed the data from the Cancer Toxicities Study and included 1636 premenopausal women with stages I-III BC who were age < 50 years and received chemotherapy but not ovarian function suppressants.

Disclosures: MA Franzoi, M Lambertini, and A Di Meglio received grants or awards for this study. Some authors declared receiving personal fees, speaking fees, grants, or honoraria from or having other ties with various sources.

Source: Kabirian R et al. Chemotherapy-related amenorrhea and quality of life among premenopausal women with breast cancer. JAMA Netw Open. 2023;6(11):e2343910 (Nov 16). doi: 10.1001/jamanetworkopen.2023.43910

Key clinical point: Chemotherapy-related amenorrhea (CRA) was common in premenopausal women with stages I-III breast cancer (BC), particularly in those who were older, experienced hot flashes, or received adjuvant tamoxifen.

Major finding: The majority (57.1%) of premenopausal patients with BC reported having persistent CRA, with the likelihood increasing in those who were age ≥ 35 years (adjusted odds ratio [aOR] 35-39 years: 1.84, 40-44 years: 5.90, ≥45 years: 21.29; all P < .001), experienced hot flashes at diagnosis (aOR 1.83; P = .01), or received adjuvant tamoxifen (aOR 1.97; P < .001).

Study details: This study analyzed the data from the Cancer Toxicities Study and included 1636 premenopausal women with stages I-III BC who were age < 50 years and received chemotherapy but not ovarian function suppressants.

Disclosures: MA Franzoi, M Lambertini, and A Di Meglio received grants or awards for this study. Some authors declared receiving personal fees, speaking fees, grants, or honoraria from or having other ties with various sources.

Source: Kabirian R et al. Chemotherapy-related amenorrhea and quality of life among premenopausal women with breast cancer. JAMA Netw Open. 2023;6(11):e2343910 (Nov 16). doi: 10.1001/jamanetworkopen.2023.43910

Key clinical point: Neoadjuvant carboplatin and docetaxel + pembrolizumab showed encouraging pathological complete response (pCR) rates and 3-year event-free survival (EFS) outcomes and had a manageable safety profile in patients with stages I-III triple-negative breast cancer (TNBC).

Major finding: The overall pCR rate was 58% (95% CI 48%-67%), with the estimated 3-year EFS rates being 86% (95% CI 77%-95%) in all patients and 98% (95% CI 95%-100%) in patients who achieved pCR. Diarrhea (4.3%), anemia (3.5%), and peripheral sensory neuropathy (2.6%) were the most common grade ≥ 3 treatment-related adverse events, and one study-related death was reported.

Study details: Findings are from the phase 2 NeoPACT trial including 115 female patients with stages I-III TNBC who received carboplatin and docetaxel + pembrolizumab in a neoadjuvant setting.

Disclosures: This study was supported by the University of Kansas Cancer Center and others. The lead author and other authors declared receiving research funding, royalties, personal, consulting or speaking fees from, being advisory board members of, or having other ties with various sources.

Source: Sharma P et al. Clinical and biomarker findings of neoadjuvant pembrolizumab and carboplatin plus docetaxel in triple-negative breast cancer: NeoPACT phase 2 clinical trial. JAMA Oncol. 2023 (Nov 22). doi: 10.1001/jamaoncol.2023.5033

Key clinical point: Neoadjuvant carboplatin and docetaxel + pembrolizumab showed encouraging pathological complete response (pCR) rates and 3-year event-free survival (EFS) outcomes and had a manageable safety profile in patients with stages I-III triple-negative breast cancer (TNBC).

Major finding: The overall pCR rate was 58% (95% CI 48%-67%), with the estimated 3-year EFS rates being 86% (95% CI 77%-95%) in all patients and 98% (95% CI 95%-100%) in patients who achieved pCR. Diarrhea (4.3%), anemia (3.5%), and peripheral sensory neuropathy (2.6%) were the most common grade ≥ 3 treatment-related adverse events, and one study-related death was reported.

Study details: Findings are from the phase 2 NeoPACT trial including 115 female patients with stages I-III TNBC who received carboplatin and docetaxel + pembrolizumab in a neoadjuvant setting.

Disclosures: This study was supported by the University of Kansas Cancer Center and others. The lead author and other authors declared receiving research funding, royalties, personal, consulting or speaking fees from, being advisory board members of, or having other ties with various sources.

Source: Sharma P et al. Clinical and biomarker findings of neoadjuvant pembrolizumab and carboplatin plus docetaxel in triple-negative breast cancer: NeoPACT phase 2 clinical trial. JAMA Oncol. 2023 (Nov 22). doi: 10.1001/jamaoncol.2023.5033

Key clinical point: Neoadjuvant carboplatin and docetaxel + pembrolizumab showed encouraging pathological complete response (pCR) rates and 3-year event-free survival (EFS) outcomes and had a manageable safety profile in patients with stages I-III triple-negative breast cancer (TNBC).

Major finding: The overall pCR rate was 58% (95% CI 48%-67%), with the estimated 3-year EFS rates being 86% (95% CI 77%-95%) in all patients and 98% (95% CI 95%-100%) in patients who achieved pCR. Diarrhea (4.3%), anemia (3.5%), and peripheral sensory neuropathy (2.6%) were the most common grade ≥ 3 treatment-related adverse events, and one study-related death was reported.

Study details: Findings are from the phase 2 NeoPACT trial including 115 female patients with stages I-III TNBC who received carboplatin and docetaxel + pembrolizumab in a neoadjuvant setting.

Disclosures: This study was supported by the University of Kansas Cancer Center and others. The lead author and other authors declared receiving research funding, royalties, personal, consulting or speaking fees from, being advisory board members of, or having other ties with various sources.

Source: Sharma P et al. Clinical and biomarker findings of neoadjuvant pembrolizumab and carboplatin plus docetaxel in triple-negative breast cancer: NeoPACT phase 2 clinical trial. JAMA Oncol. 2023 (Nov 22). doi: 10.1001/jamaoncol.2023.5033

Key clinical point: Women with apparently unifocal, non–triple-negative breast cancer (BC) who underwent preoperative magnetic resonance imaging (MRI) and did not have any occult malignancy may safely forgo radiation therapy.

Major finding: Preoperative MRI detected malignant occult lesions in 11% of patients with BC. At 5 years, the ipsilateral invasive recurrence rate was very low (1.0%; upper 95% CI 5.4%) in patients with no occult malignancy who did not receive adjuvant radiotherapy.

Study details: Findings are from the prospective 2-arm PROSPECT study that included 443 patients with non–triple-negative, clinical stage T1N0, apparently unifocal BC who underwent MRI, of whom 201 patients underwent breast-conserving surgery without radiotherapy and 242 women were deemed ineligible for radiotherapy omission.

Disclosures: This study was funded by the Breast Cancer Trials, Australia, and other sources. The authors declared no conflicts of interest.

Source: Mann GB et al. Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): Primary results of a prospective two-arm study. Lancet. 2023 (Dec 5). doi: 10.1016/S0140-6736(23)02476-5

Key clinical point: Women with apparently unifocal, non–triple-negative breast cancer (BC) who underwent preoperative magnetic resonance imaging (MRI) and did not have any occult malignancy may safely forgo radiation therapy.

Major finding: Preoperative MRI detected malignant occult lesions in 11% of patients with BC. At 5 years, the ipsilateral invasive recurrence rate was very low (1.0%; upper 95% CI 5.4%) in patients with no occult malignancy who did not receive adjuvant radiotherapy.

Study details: Findings are from the prospective 2-arm PROSPECT study that included 443 patients with non–triple-negative, clinical stage T1N0, apparently unifocal BC who underwent MRI, of whom 201 patients underwent breast-conserving surgery without radiotherapy and 242 women were deemed ineligible for radiotherapy omission.

Disclosures: This study was funded by the Breast Cancer Trials, Australia, and other sources. The authors declared no conflicts of interest.

Source: Mann GB et al. Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): Primary results of a prospective two-arm study. Lancet. 2023 (Dec 5). doi: 10.1016/S0140-6736(23)02476-5

Key clinical point: Women with apparently unifocal, non–triple-negative breast cancer (BC) who underwent preoperative magnetic resonance imaging (MRI) and did not have any occult malignancy may safely forgo radiation therapy.

Major finding: Preoperative MRI detected malignant occult lesions in 11% of patients with BC. At 5 years, the ipsilateral invasive recurrence rate was very low (1.0%; upper 95% CI 5.4%) in patients with no occult malignancy who did not receive adjuvant radiotherapy.

Study details: Findings are from the prospective 2-arm PROSPECT study that included 443 patients with non–triple-negative, clinical stage T1N0, apparently unifocal BC who underwent MRI, of whom 201 patients underwent breast-conserving surgery without radiotherapy and 242 women were deemed ineligible for radiotherapy omission.

Disclosures: This study was funded by the Breast Cancer Trials, Australia, and other sources. The authors declared no conflicts of interest.

Source: Mann GB et al. Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): Primary results of a prospective two-arm study. Lancet. 2023 (Dec 5). doi: 10.1016/S0140-6736(23)02476-5

Key clinical point: The post-diagnostic use of statins lowered the risk for mortality in patients with newly diagnosed breast cancer (BC) only in case of a subsequent lowering of serum cholesterol levels.

Major finding: Compared with patients who did not receive statins, the risk for BC-specific mortality was significantly reduced in those who received statins after BC diagnosis and reported a subsequent reduction in the median total cholesterol level (adjusted hazard ratio 0.49; P = .001). No mortality-risk reduction was observed in patients whose cholesterol levels did not decrease after the post-diagnostic initiation of statins (P = .30).

Study details: This retrospective population-based cohort study included 13,378 patients with newly diagnosed invasive BC, of whom 980 patients initiated statins after BC diagnosis.

Disclosures: This study was supported by research funds and a grant from the Pirkanmaa Hospital District and Duodecim, Finland, respectively. Two authors declared receiving grants or personal fees from various sources, including the Pirkanmaa Hospital District. The other authors declared no conflicts of interest.

Source: Murto MO et al. Statin use, cholesterol level, and mortality among females with breast cancer. JAMA Netw Open. 2023;6(11):e2343861 (Nov 17). doi: 10.1001/jamanetworkopen.2023.43861

Key clinical point: The post-diagnostic use of statins lowered the risk for mortality in patients with newly diagnosed breast cancer (BC) only in case of a subsequent lowering of serum cholesterol levels.

Major finding: Compared with patients who did not receive statins, the risk for BC-specific mortality was significantly reduced in those who received statins after BC diagnosis and reported a subsequent reduction in the median total cholesterol level (adjusted hazard ratio 0.49; P = .001). No mortality-risk reduction was observed in patients whose cholesterol levels did not decrease after the post-diagnostic initiation of statins (P = .30).

Study details: This retrospective population-based cohort study included 13,378 patients with newly diagnosed invasive BC, of whom 980 patients initiated statins after BC diagnosis.

Disclosures: This study was supported by research funds and a grant from the Pirkanmaa Hospital District and Duodecim, Finland, respectively. Two authors declared receiving grants or personal fees from various sources, including the Pirkanmaa Hospital District. The other authors declared no conflicts of interest.

Source: Murto MO et al. Statin use, cholesterol level, and mortality among females with breast cancer. JAMA Netw Open. 2023;6(11):e2343861 (Nov 17). doi: 10.1001/jamanetworkopen.2023.43861

Key clinical point: The post-diagnostic use of statins lowered the risk for mortality in patients with newly diagnosed breast cancer (BC) only in case of a subsequent lowering of serum cholesterol levels.

Major finding: Compared with patients who did not receive statins, the risk for BC-specific mortality was significantly reduced in those who received statins after BC diagnosis and reported a subsequent reduction in the median total cholesterol level (adjusted hazard ratio 0.49; P = .001). No mortality-risk reduction was observed in patients whose cholesterol levels did not decrease after the post-diagnostic initiation of statins (P = .30).

Study details: This retrospective population-based cohort study included 13,378 patients with newly diagnosed invasive BC, of whom 980 patients initiated statins after BC diagnosis.

Disclosures: This study was supported by research funds and a grant from the Pirkanmaa Hospital District and Duodecim, Finland, respectively. Two authors declared receiving grants or personal fees from various sources, including the Pirkanmaa Hospital District. The other authors declared no conflicts of interest.

Source: Murto MO et al. Statin use, cholesterol level, and mortality among females with breast cancer. JAMA Netw Open. 2023;6(11):e2343861 (Nov 17). doi: 10.1001/jamanetworkopen.2023.43861

Key clinical point: Pemetrexed + vinorelbine vs vinorelbine monotherapy led to a greater improvement in progression-free survival (PFS) outcomes and had a manageable safety profile in patients with metastatic breast cancer (BC) previously treated with anthracycline and taxane.

Major finding: The median PFS improved by 45% with pemetrexed + vinorelbine vs vinorelbine monotherapy (5.7 vs 1.6 months; hazard ratio 0.55; P = .001). Pemetrexed + vinorelbine also had a manageable safety profile in general.

Study details: Findings are from the phase 2 KCSG-BR15-17 trial including 125 patients with metastatic BC who had been treated with anthracycline and taxane previously and were randomly assigned to receive pemetrexed + vinorelbine or vinorelbine monotherapy.

Disclosures: This study was funded by a grant from the Ministry of Health and Welfare, Republic of Korea. Two authors declared receiving research funding or research drug supply from or serving in consulting or advisory roles for various sources. The other authors declared no conflicts of interest.

Source: Lee DW, Jung KH, et al. Pemetrexed plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer (KCSG-BR15-17): A randomized, open label, multicenter, phase II trial. Eur J Cancer. 2023;113456 (Nov 20). doi: 10.1016/j.ejca.2023.113456

Key clinical point: Pemetrexed + vinorelbine vs vinorelbine monotherapy led to a greater improvement in progression-free survival (PFS) outcomes and had a manageable safety profile in patients with metastatic breast cancer (BC) previously treated with anthracycline and taxane.

Major finding: The median PFS improved by 45% with pemetrexed + vinorelbine vs vinorelbine monotherapy (5.7 vs 1.6 months; hazard ratio 0.55; P = .001). Pemetrexed + vinorelbine also had a manageable safety profile in general.

Study details: Findings are from the phase 2 KCSG-BR15-17 trial including 125 patients with metastatic BC who had been treated with anthracycline and taxane previously and were randomly assigned to receive pemetrexed + vinorelbine or vinorelbine monotherapy.

Disclosures: This study was funded by a grant from the Ministry of Health and Welfare, Republic of Korea. Two authors declared receiving research funding or research drug supply from or serving in consulting or advisory roles for various sources. The other authors declared no conflicts of interest.

Source: Lee DW, Jung KH, et al. Pemetrexed plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer (KCSG-BR15-17): A randomized, open label, multicenter, phase II trial. Eur J Cancer. 2023;113456 (Nov 20). doi: 10.1016/j.ejca.2023.113456

Key clinical point: Pemetrexed + vinorelbine vs vinorelbine monotherapy led to a greater improvement in progression-free survival (PFS) outcomes and had a manageable safety profile in patients with metastatic breast cancer (BC) previously treated with anthracycline and taxane.

Major finding: The median PFS improved by 45% with pemetrexed + vinorelbine vs vinorelbine monotherapy (5.7 vs 1.6 months; hazard ratio 0.55; P = .001). Pemetrexed + vinorelbine also had a manageable safety profile in general.

Study details: Findings are from the phase 2 KCSG-BR15-17 trial including 125 patients with metastatic BC who had been treated with anthracycline and taxane previously and were randomly assigned to receive pemetrexed + vinorelbine or vinorelbine monotherapy.

Disclosures: This study was funded by a grant from the Ministry of Health and Welfare, Republic of Korea. Two authors declared receiving research funding or research drug supply from or serving in consulting or advisory roles for various sources. The other authors declared no conflicts of interest.

Source: Lee DW, Jung KH, et al. Pemetrexed plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer (KCSG-BR15-17): A randomized, open label, multicenter, phase II trial. Eur J Cancer. 2023;113456 (Nov 20). doi: 10.1016/j.ejca.2023.113456

Key clinical point: Women with germline BRCA1 or BRCA2 pathogenic mutations who had a pregnancy after diagnosis of early breast cancer (BC) reported prognostic outcomes similar to that of women without a pregnancy.

Major finding: The cumulative incidence of pregnancy was 22% at 10 years. The disease-free survival outcomes were comparable between patients with BC who did vs did not become pregnant (adjusted hazard ratio 0.99; P = .90).

Study details: Findings are from a retrospective cohort study including 4732 young women age ≤ 40 years with a history of BC who had germline pathogenic BRCA mutations, of whom 659 women reported ≥1 pregnancy after BC.

Disclosures: The study was partly supported by the Italian Association for Cancer Research and the 2022 Gilead Research Scholars Program in Solid Tumors. The authors declared receiving speaker honoraria, travel grants, research funding, or speaker fees from and having other ties with Gilead and several other sources.

Source: Lambertini M et al. Pregnancy after breast cancer in young BRCA carriers: An international hospital-based cohort study. JAMA. 2023 (Dec 7). doi: 10.1001/jama.2023.25463

Key clinical point: Women with germline BRCA1 or BRCA2 pathogenic mutations who had a pregnancy after diagnosis of early breast cancer (BC) reported prognostic outcomes similar to that of women without a pregnancy.

Major finding: The cumulative incidence of pregnancy was 22% at 10 years. The disease-free survival outcomes were comparable between patients with BC who did vs did not become pregnant (adjusted hazard ratio 0.99; P = .90).

Study details: Findings are from a retrospective cohort study including 4732 young women age ≤ 40 years with a history of BC who had germline pathogenic BRCA mutations, of whom 659 women reported ≥1 pregnancy after BC.

Disclosures: The study was partly supported by the Italian Association for Cancer Research and the 2022 Gilead Research Scholars Program in Solid Tumors. The authors declared receiving speaker honoraria, travel grants, research funding, or speaker fees from and having other ties with Gilead and several other sources.

Source: Lambertini M et al. Pregnancy after breast cancer in young BRCA carriers: An international hospital-based cohort study. JAMA. 2023 (Dec 7). doi: 10.1001/jama.2023.25463

Key clinical point: Women with germline BRCA1 or BRCA2 pathogenic mutations who had a pregnancy after diagnosis of early breast cancer (BC) reported prognostic outcomes similar to that of women without a pregnancy.

Major finding: The cumulative incidence of pregnancy was 22% at 10 years. The disease-free survival outcomes were comparable between patients with BC who did vs did not become pregnant (adjusted hazard ratio 0.99; P = .90).

Study details: Findings are from a retrospective cohort study including 4732 young women age ≤ 40 years with a history of BC who had germline pathogenic BRCA mutations, of whom 659 women reported ≥1 pregnancy after BC.

Disclosures: The study was partly supported by the Italian Association for Cancer Research and the 2022 Gilead Research Scholars Program in Solid Tumors. The authors declared receiving speaker honoraria, travel grants, research funding, or speaker fees from and having other ties with Gilead and several other sources.

Source: Lambertini M et al. Pregnancy after breast cancer in young BRCA carriers: An international hospital-based cohort study. JAMA. 2023 (Dec 7). doi: 10.1001/jama.2023.25463

In September 2023, Goldman et al. published a communication in Dermatologic Surgery describing their use of subcutaneous sodium deoxycholate injection (SDOC), with or without triamcinolone acetonide, for reduction of submental fat.Because of the variability and severity of postprocedure edema with SDOC treatment, they hypothesized that injection of triamcinolone in conjunction with SDOC (Kybella) would improve posttreatment edema and patient tolerability.

As they note, “patients experience a variable degree of edema and discomfort following subcutaneous injection,” of SDOC, something that I and others have also observed in our practices.

In their double-blind study of 20 patients with a baseline Clinician-Reported Submental Fat Rating Scale of 2 or 3 out of 4, 5 patients were randomized to receive SDOC as recommended in the label, while 15 received SDOC plus triamcinolone. In the latter group, 2 mL of SDOC was mixed with 0.5 mL of 40 mg/mL of triamcinolone acetate, then administered in up to 50 injections in the submentum spaced 1.0 cm apart at 0.25 mL per injection. Three treatments were administered 1 month apart.

For both groups, volumes between 5 mL and 8 mL per treatment were delivered. There were no significant differences in efficacy 30, 60, and 90 days after the final injection between the two groups. However, at day 180, the group that received only SDOC had a significantly greater reduction in submental fat, which the authors wrote indicated that the addition of triamcinolone “may mildly diminish the fat reduction effects” at that time point.

Subcutaneous SDOC (deoxycholic acid) injections for reduction of submental fullness was approved by the Food and Drug Administration in 2015 for improving the appearance of moderate to severe convexity or fullness associated with submental fat in adults. (I was involved in the clinical trials.) We found that in the trial, for optimal efficacy, most patients require two to four treatments spread at least a month apart, with patients who had larger treatment areas requiring up to six treatments.

While the clinical trial treatments were spaced 4 weeks apart, post approval, we found that patients would sometimes report further efficacy even 2-3 months post injection. Since not everyone wants to go around with edema every month for 2-4 consecutive months, spacing the treatments farther apart allows patients more time to heal and coordinate the recovery appearance around their work and social schedules.

In my practice, very rarely have we seen minimal to moderate prolonged edema, particularly in younger patients, beyond 1 month post injection. Most people have the most noticeable edema — the “bull-frog” appearance — for the first 1-3 days, with some minor fullness that appears to be almost back to baseline at 1 week. In some of these patients with prolonged submental fullness, it looks fuller than it appeared pretreatment even months afterwards.

While rare, like the study authors, I have found intralesional triamcinolone to be helpful at reducing this persistent fullness should it occur. It is likely to be reducing any persistent inflammation or posttreatment fibrosis in these patients.

Unlike the study authors, I do not combine SDOC and triamcinolone injections at the time of treatment. Rather, I consider injecting triamcinolone if submental fullness is greater than at baseline or edema persists after SDOC treatment. It is rare that I’ve had to do this, as most cases self-resolve, but I have used triamcinolone 10 mg/mL, up to 1cc total, injected 6-8 weeks apart one to three times to the affected area and found it to be effective if fullness has persisted beyond 6 months. Liposuction may also be an option, if needed, if fullness/edema persists.

Overall, SDOC is an effective treatment for small pockets of subcutaneous fat. Approved for submental fullness, it is now sometimes used off-label for other parts of the body, such as bra fat, small pockets of the abdomen, and lipomas. While some inflammation after treatment is expected — and desired — to achieve an effective outcome of fat apoptosis, intralesional triamcinolone is an interesting tool to utilize should inflammation or posttreatment fullness persist.

Dr. Wesley practices dermatology in Beverly Hills, California. Write to her at [email protected]. She was an investigator in clinical trials of Kybella.

In September 2023, Goldman et al. published a communication in Dermatologic Surgery describing their use of subcutaneous sodium deoxycholate injection (SDOC), with or without triamcinolone acetonide, for reduction of submental fat.Because of the variability and severity of postprocedure edema with SDOC treatment, they hypothesized that injection of triamcinolone in conjunction with SDOC (Kybella) would improve posttreatment edema and patient tolerability.

As they note, “patients experience a variable degree of edema and discomfort following subcutaneous injection,” of SDOC, something that I and others have also observed in our practices.

In their double-blind study of 20 patients with a baseline Clinician-Reported Submental Fat Rating Scale of 2 or 3 out of 4, 5 patients were randomized to receive SDOC as recommended in the label, while 15 received SDOC plus triamcinolone. In the latter group, 2 mL of SDOC was mixed with 0.5 mL of 40 mg/mL of triamcinolone acetate, then administered in up to 50 injections in the submentum spaced 1.0 cm apart at 0.25 mL per injection. Three treatments were administered 1 month apart.

For both groups, volumes between 5 mL and 8 mL per treatment were delivered. There were no significant differences in efficacy 30, 60, and 90 days after the final injection between the two groups. However, at day 180, the group that received only SDOC had a significantly greater reduction in submental fat, which the authors wrote indicated that the addition of triamcinolone “may mildly diminish the fat reduction effects” at that time point.

Subcutaneous SDOC (deoxycholic acid) injections for reduction of submental fullness was approved by the Food and Drug Administration in 2015 for improving the appearance of moderate to severe convexity or fullness associated with submental fat in adults. (I was involved in the clinical trials.) We found that in the trial, for optimal efficacy, most patients require two to four treatments spread at least a month apart, with patients who had larger treatment areas requiring up to six treatments.

While the clinical trial treatments were spaced 4 weeks apart, post approval, we found that patients would sometimes report further efficacy even 2-3 months post injection. Since not everyone wants to go around with edema every month for 2-4 consecutive months, spacing the treatments farther apart allows patients more time to heal and coordinate the recovery appearance around their work and social schedules.

In my practice, very rarely have we seen minimal to moderate prolonged edema, particularly in younger patients, beyond 1 month post injection. Most people have the most noticeable edema — the “bull-frog” appearance — for the first 1-3 days, with some minor fullness that appears to be almost back to baseline at 1 week. In some of these patients with prolonged submental fullness, it looks fuller than it appeared pretreatment even months afterwards.

While rare, like the study authors, I have found intralesional triamcinolone to be helpful at reducing this persistent fullness should it occur. It is likely to be reducing any persistent inflammation or posttreatment fibrosis in these patients.

Unlike the study authors, I do not combine SDOC and triamcinolone injections at the time of treatment. Rather, I consider injecting triamcinolone if submental fullness is greater than at baseline or edema persists after SDOC treatment. It is rare that I’ve had to do this, as most cases self-resolve, but I have used triamcinolone 10 mg/mL, up to 1cc total, injected 6-8 weeks apart one to three times to the affected area and found it to be effective if fullness has persisted beyond 6 months. Liposuction may also be an option, if needed, if fullness/edema persists.

Overall, SDOC is an effective treatment for small pockets of subcutaneous fat. Approved for submental fullness, it is now sometimes used off-label for other parts of the body, such as bra fat, small pockets of the abdomen, and lipomas. While some inflammation after treatment is expected — and desired — to achieve an effective outcome of fat apoptosis, intralesional triamcinolone is an interesting tool to utilize should inflammation or posttreatment fullness persist.

Dr. Wesley practices dermatology in Beverly Hills, California. Write to her at [email protected]. She was an investigator in clinical trials of Kybella.

In September 2023, Goldman et al. published a communication in Dermatologic Surgery describing their use of subcutaneous sodium deoxycholate injection (SDOC), with or without triamcinolone acetonide, for reduction of submental fat.Because of the variability and severity of postprocedure edema with SDOC treatment, they hypothesized that injection of triamcinolone in conjunction with SDOC (Kybella) would improve posttreatment edema and patient tolerability.

As they note, “patients experience a variable degree of edema and discomfort following subcutaneous injection,” of SDOC, something that I and others have also observed in our practices.

In their double-blind study of 20 patients with a baseline Clinician-Reported Submental Fat Rating Scale of 2 or 3 out of 4, 5 patients were randomized to receive SDOC as recommended in the label, while 15 received SDOC plus triamcinolone. In the latter group, 2 mL of SDOC was mixed with 0.5 mL of 40 mg/mL of triamcinolone acetate, then administered in up to 50 injections in the submentum spaced 1.0 cm apart at 0.25 mL per injection. Three treatments were administered 1 month apart.

For both groups, volumes between 5 mL and 8 mL per treatment were delivered. There were no significant differences in efficacy 30, 60, and 90 days after the final injection between the two groups. However, at day 180, the group that received only SDOC had a significantly greater reduction in submental fat, which the authors wrote indicated that the addition of triamcinolone “may mildly diminish the fat reduction effects” at that time point.

Subcutaneous SDOC (deoxycholic acid) injections for reduction of submental fullness was approved by the Food and Drug Administration in 2015 for improving the appearance of moderate to severe convexity or fullness associated with submental fat in adults. (I was involved in the clinical trials.) We found that in the trial, for optimal efficacy, most patients require two to four treatments spread at least a month apart, with patients who had larger treatment areas requiring up to six treatments.

While the clinical trial treatments were spaced 4 weeks apart, post approval, we found that patients would sometimes report further efficacy even 2-3 months post injection. Since not everyone wants to go around with edema every month for 2-4 consecutive months, spacing the treatments farther apart allows patients more time to heal and coordinate the recovery appearance around their work and social schedules.

In my practice, very rarely have we seen minimal to moderate prolonged edema, particularly in younger patients, beyond 1 month post injection. Most people have the most noticeable edema — the “bull-frog” appearance — for the first 1-3 days, with some minor fullness that appears to be almost back to baseline at 1 week. In some of these patients with prolonged submental fullness, it looks fuller than it appeared pretreatment even months afterwards.

While rare, like the study authors, I have found intralesional triamcinolone to be helpful at reducing this persistent fullness should it occur. It is likely to be reducing any persistent inflammation or posttreatment fibrosis in these patients.

Unlike the study authors, I do not combine SDOC and triamcinolone injections at the time of treatment. Rather, I consider injecting triamcinolone if submental fullness is greater than at baseline or edema persists after SDOC treatment. It is rare that I’ve had to do this, as most cases self-resolve, but I have used triamcinolone 10 mg/mL, up to 1cc total, injected 6-8 weeks apart one to three times to the affected area and found it to be effective if fullness has persisted beyond 6 months. Liposuction may also be an option, if needed, if fullness/edema persists.

Overall, SDOC is an effective treatment for small pockets of subcutaneous fat. Approved for submental fullness, it is now sometimes used off-label for other parts of the body, such as bra fat, small pockets of the abdomen, and lipomas. While some inflammation after treatment is expected — and desired — to achieve an effective outcome of fat apoptosis, intralesional triamcinolone is an interesting tool to utilize should inflammation or posttreatment fullness persist.

Dr. Wesley practices dermatology in Beverly Hills, California. Write to her at [email protected]. She was an investigator in clinical trials of Kybella.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are associated with a reduced risk for colorectal cancer (CRC) in patients with type 2 diabetes, with and without overweight or obesity, according to a new analysis.

In particular, GLP-1 RAs were associated with decreased risk compared with other antidiabetic treatments, including insulin, metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, sulfonylureas, and thiazolidinediones.

More profound effects were seen in patients with overweight or obesity, “suggesting a potential protective effect against CRC partially mediated by weight loss and other mechanisms related to weight loss,” Lindsey Wang, an undergraduate student at Case Western Reserve University, Cleveland, Ohio, and colleagues wrote in JAMA Oncology.
 

Testing Treatments

GLP-1 RAs, usually given by injection, are approved by the US Food and Drug Administration to treat type 2 diabetes. They can lower blood sugar levels, improve insulin sensitivity, and help patients manage their weight.

Diabetes, overweight, and obesity are known risk factors for CRC and make prognosis worse. Ms. Wang and colleagues hypothesized that GLP-1 RAs might reduce CRC risk compared with other antidiabetics, including metformin and insulin, which have also been shown to reduce CRC risk.

Using a national database of more than 101 million electronic health records, Ms. Wang and colleagues conducted a population-based study of more than 1.2 million patients who had medical encounters for type 2 diabetes and were subsequently prescribed antidiabetic medications between 2005 and 2019. The patients had no prior antidiabetic medication use nor CRC diagnosis.

The researchers analyzed the effects of GLP-1 RAs on CRC incidence compared with the other prescribed antidiabetic drugs, matching for demographics, adverse socioeconomic determinants of health, preexisting medical conditions, family and personal history of cancers and colonic polyps, lifestyle factors, and procedures such as colonoscopy.

During a 15-year follow-up, GLP-1 RAs were associated with decreased risk for CRC compared with insulin (hazard ratio [HR], 0.56), metformin (HR, 0.75), SGLT2 inhibitors (HR, 0.77), sulfonylureas (HR, 0.82), and thiazolidinediones (HR, 0.82) in the overall study population.

For instance, among 22,572 patients who took insulin, 167 cases of CRC occurred, compared with 94 cases among the matched GLP-1 RA cohort. Among 18,518 patients who took metformin, 153 cases of CRC occurred compared with 96 cases among the matched GLP-1 RA cohort.

GLP-1 RAs also were associated with lower but not statistically significant risk than alpha-glucosidase inhibitors (HR, 0.59) and dipeptidyl-peptidase-4 (DPP-4) inhibitors (HR, 0.93).

In patients with overweight or obesity, GLP-1 RAs were associated with a lower risk for CRC than most of the other antidiabetics, including insulin (HR, 0.5), metformin (HR, 0.58), SGLT2 inhibitors (HR, 0.68), sulfonylureas (HR, 0.63), thiazolidinediones (HR, 0.73), and DPP-4 inhibitors (HR, 0.77).

Consistent findings were observed in women and men.

“Our results clearly demonstrate that GLP-1 RAs are significantly more effective than popular antidiabetic drugs, such as metformin or insulin, at preventing the development of CRC,” said Nathan Berger, MD, co-lead researcher, professor of experimental medicine, and member of the Case Comprehensive Cancer Center.
 

Targets for Future Research

Study limitations include potential unmeasured or uncontrolled confounders, self-selection, reverse causality, and other biases involved in observational studies, the research team noted.

Further research is warranted to investigate the effects in patients with prior antidiabetic treatments, underlying mechanisms, potential variation in effects among different GLP-1 RAs, and the potential of GLP-1 RAs to reduce the risks for other obesity-associated cancers, the researchers wrote.

“To our knowledge, this is the first indication this popular weight loss and antidiabetic class of drugs reduces incidence of CRC, relative to other antidiabetic agents,” said Rong Xu, PhD, co-lead researcher, professor of medicine, and member of the Case Comprehensive Cancer Center.

The study was supported by the National Cancer Institute Case Comprehensive Cancer Center, American Cancer Society, Landon Foundation-American Association for Cancer Research, National Institutes of Health Director’s New Innovator Award Program, National Institute on Aging, and National Institute on Alcohol Abuse and Alcoholism. Several authors reported grants from the National Institutes of Health during the conduct of the study.
 

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are associated with a reduced risk for colorectal cancer (CRC) in patients with type 2 diabetes, with and without overweight or obesity, according to a new analysis.

In particular, GLP-1 RAs were associated with decreased risk compared with other antidiabetic treatments, including insulin, metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, sulfonylureas, and thiazolidinediones.

More profound effects were seen in patients with overweight or obesity, “suggesting a potential protective effect against CRC partially mediated by weight loss and other mechanisms related to weight loss,” Lindsey Wang, an undergraduate student at Case Western Reserve University, Cleveland, Ohio, and colleagues wrote in JAMA Oncology.
 

Testing Treatments

GLP-1 RAs, usually given by injection, are approved by the US Food and Drug Administration to treat type 2 diabetes. They can lower blood sugar levels, improve insulin sensitivity, and help patients manage their weight.

Diabetes, overweight, and obesity are known risk factors for CRC and make prognosis worse. Ms. Wang and colleagues hypothesized that GLP-1 RAs might reduce CRC risk compared with other antidiabetics, including metformin and insulin, which have also been shown to reduce CRC risk.

Using a national database of more than 101 million electronic health records, Ms. Wang and colleagues conducted a population-based study of more than 1.2 million patients who had medical encounters for type 2 diabetes and were subsequently prescribed antidiabetic medications between 2005 and 2019. The patients had no prior antidiabetic medication use nor CRC diagnosis.

The researchers analyzed the effects of GLP-1 RAs on CRC incidence compared with the other prescribed antidiabetic drugs, matching for demographics, adverse socioeconomic determinants of health, preexisting medical conditions, family and personal history of cancers and colonic polyps, lifestyle factors, and procedures such as colonoscopy.

During a 15-year follow-up, GLP-1 RAs were associated with decreased risk for CRC compared with insulin (hazard ratio [HR], 0.56), metformin (HR, 0.75), SGLT2 inhibitors (HR, 0.77), sulfonylureas (HR, 0.82), and thiazolidinediones (HR, 0.82) in the overall study population.

For instance, among 22,572 patients who took insulin, 167 cases of CRC occurred, compared with 94 cases among the matched GLP-1 RA cohort. Among 18,518 patients who took metformin, 153 cases of CRC occurred compared with 96 cases among the matched GLP-1 RA cohort.

GLP-1 RAs also were associated with lower but not statistically significant risk than alpha-glucosidase inhibitors (HR, 0.59) and dipeptidyl-peptidase-4 (DPP-4) inhibitors (HR, 0.93).

In patients with overweight or obesity, GLP-1 RAs were associated with a lower risk for CRC than most of the other antidiabetics, including insulin (HR, 0.5), metformin (HR, 0.58), SGLT2 inhibitors (HR, 0.68), sulfonylureas (HR, 0.63), thiazolidinediones (HR, 0.73), and DPP-4 inhibitors (HR, 0.77).

Consistent findings were observed in women and men.

“Our results clearly demonstrate that GLP-1 RAs are significantly more effective than popular antidiabetic drugs, such as metformin or insulin, at preventing the development of CRC,” said Nathan Berger, MD, co-lead researcher, professor of experimental medicine, and member of the Case Comprehensive Cancer Center.
 

Targets for Future Research

Study limitations include potential unmeasured or uncontrolled confounders, self-selection, reverse causality, and other biases involved in observational studies, the research team noted.

Further research is warranted to investigate the effects in patients with prior antidiabetic treatments, underlying mechanisms, potential variation in effects among different GLP-1 RAs, and the potential of GLP-1 RAs to reduce the risks for other obesity-associated cancers, the researchers wrote.

“To our knowledge, this is the first indication this popular weight loss and antidiabetic class of drugs reduces incidence of CRC, relative to other antidiabetic agents,” said Rong Xu, PhD, co-lead researcher, professor of medicine, and member of the Case Comprehensive Cancer Center.

The study was supported by the National Cancer Institute Case Comprehensive Cancer Center, American Cancer Society, Landon Foundation-American Association for Cancer Research, National Institutes of Health Director’s New Innovator Award Program, National Institute on Aging, and National Institute on Alcohol Abuse and Alcoholism. Several authors reported grants from the National Institutes of Health during the conduct of the study.
 

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are associated with a reduced risk for colorectal cancer (CRC) in patients with type 2 diabetes, with and without overweight or obesity, according to a new analysis.

In particular, GLP-1 RAs were associated with decreased risk compared with other antidiabetic treatments, including insulin, metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, sulfonylureas, and thiazolidinediones.

More profound effects were seen in patients with overweight or obesity, “suggesting a potential protective effect against CRC partially mediated by weight loss and other mechanisms related to weight loss,” Lindsey Wang, an undergraduate student at Case Western Reserve University, Cleveland, Ohio, and colleagues wrote in JAMA Oncology.
 

Testing Treatments

GLP-1 RAs, usually given by injection, are approved by the US Food and Drug Administration to treat type 2 diabetes. They can lower blood sugar levels, improve insulin sensitivity, and help patients manage their weight.

Diabetes, overweight, and obesity are known risk factors for CRC and make prognosis worse. Ms. Wang and colleagues hypothesized that GLP-1 RAs might reduce CRC risk compared with other antidiabetics, including metformin and insulin, which have also been shown to reduce CRC risk.

Using a national database of more than 101 million electronic health records, Ms. Wang and colleagues conducted a population-based study of more than 1.2 million patients who had medical encounters for type 2 diabetes and were subsequently prescribed antidiabetic medications between 2005 and 2019. The patients had no prior antidiabetic medication use nor CRC diagnosis.

The researchers analyzed the effects of GLP-1 RAs on CRC incidence compared with the other prescribed antidiabetic drugs, matching for demographics, adverse socioeconomic determinants of health, preexisting medical conditions, family and personal history of cancers and colonic polyps, lifestyle factors, and procedures such as colonoscopy.

During a 15-year follow-up, GLP-1 RAs were associated with decreased risk for CRC compared with insulin (hazard ratio [HR], 0.56), metformin (HR, 0.75), SGLT2 inhibitors (HR, 0.77), sulfonylureas (HR, 0.82), and thiazolidinediones (HR, 0.82) in the overall study population.

For instance, among 22,572 patients who took insulin, 167 cases of CRC occurred, compared with 94 cases among the matched GLP-1 RA cohort. Among 18,518 patients who took metformin, 153 cases of CRC occurred compared with 96 cases among the matched GLP-1 RA cohort.

GLP-1 RAs also were associated with lower but not statistically significant risk than alpha-glucosidase inhibitors (HR, 0.59) and dipeptidyl-peptidase-4 (DPP-4) inhibitors (HR, 0.93).

In patients with overweight or obesity, GLP-1 RAs were associated with a lower risk for CRC than most of the other antidiabetics, including insulin (HR, 0.5), metformin (HR, 0.58), SGLT2 inhibitors (HR, 0.68), sulfonylureas (HR, 0.63), thiazolidinediones (HR, 0.73), and DPP-4 inhibitors (HR, 0.77).

Consistent findings were observed in women and men.

“Our results clearly demonstrate that GLP-1 RAs are significantly more effective than popular antidiabetic drugs, such as metformin or insulin, at preventing the development of CRC,” said Nathan Berger, MD, co-lead researcher, professor of experimental medicine, and member of the Case Comprehensive Cancer Center.
 

Targets for Future Research

Study limitations include potential unmeasured or uncontrolled confounders, self-selection, reverse causality, and other biases involved in observational studies, the research team noted.

Further research is warranted to investigate the effects in patients with prior antidiabetic treatments, underlying mechanisms, potential variation in effects among different GLP-1 RAs, and the potential of GLP-1 RAs to reduce the risks for other obesity-associated cancers, the researchers wrote.

“To our knowledge, this is the first indication this popular weight loss and antidiabetic class of drugs reduces incidence of CRC, relative to other antidiabetic agents,” said Rong Xu, PhD, co-lead researcher, professor of medicine, and member of the Case Comprehensive Cancer Center.

The study was supported by the National Cancer Institute Case Comprehensive Cancer Center, American Cancer Society, Landon Foundation-American Association for Cancer Research, National Institutes of Health Director’s New Innovator Award Program, National Institute on Aging, and National Institute on Alcohol Abuse and Alcoholism. Several authors reported grants from the National Institutes of Health during the conduct of the study.
 

A version of this article appeared on Medscape.com.

Earlier this month, the U.S. Food and Drug Administration (FDA) approved two gene-editing therapies for patients aged 12 years or older with severe sickle cell disease.

One therapy — exagamglogene autotemcel or exa-cel (Casgevy) — is the first to use CRISPR gene-editing technology, and could “provide a one-time functional cure to patients with sickle cell disease,” said Haydar Frangoul, MD, of The Children’s Hospital at TriStar Centennial, Nashville, Tennessee.

Dr. Frangoul, who presented a recent interim analysis on the therapy at the American Society of Hematology (ASH) annual meeting earlier this month, reported that one infusion of exa-cel prompted rapid increases in total hemoglobin levels and almost completely eliminated a common and painful complication of sickle cell disease that can lead to irreversible organ damage, known as vaso-occlusive crisis.

Overall, the gene therapy led to “a rapid, robust, and durable increase in total hemoglobin to normal or near normal levels,” Dr. Frangoul said.

Exa-cel, from Vertex Pharmaceuticals and CRISPR Therapeutics, is a single-dose infusion containing a patient’s modified cells. First, a patient’s stem cells are harvested and then genetically modified to produce fetal hemoglobin. 

The development of exa-cel was “grounded in human genetics, which show that fetal hemoglobin can substitute for sickle hemoglobin,” Dr. Frangoul explained. Patients receive these edited cells, which then help restore normal hemoglobin production.

The analysis showed that a one-time infusion of exa-cel following myeloablative conditioning prevented vaso-occlusive crisis in all but one patient with severe sickle cell disease. The therapy also prevented inpatient hospitalizations for vaso-occlusive crisis in all patients and led to sustained improvements in quality of life.

The results are “really striking,” said Sarah H. O’Brien, MD, of Nationwide Children’s Hospital in Columbus, Ohio, who was not involved in the research. “The majority of our admissions on the hematology service are our patients with sickle cell. They’re uncomfortable, they’re in pain, they’re missing school, and they’re missing their activities,” which makes these interim findings quite “impactful.”

To examine the impact of exa-cel on vaso-occlusive crisis, the phase 3 trial included individuals aged 12 to 35 years with severe sickle cell disease and a history of at least two vaso-occlusive crises per year over the past 2 years.

Participants underwent cell CD34+ stem cell collection. These cells then underwent gene editing using CRISPR technology, explained Dr. Frangoul.

At the transplant center, patients received myeloablative conditioning chemotherapy with busulfan for 4 days before receiving an exa-cel infusion.

At the data cutoff in June 2023, 44 patients had been enrolled, of whom 30 were available for efficacy analysis. The mean age at screening was 22.1 years, and almost half (46.7%) were female. Prior to study recruitment, patients had a mean of 3.9 vaso-occlusive crises per year and a mean of 2.7 inpatient hospitalizations per year for severe vaso-occlusive crisis.

All but one patient (96.7%) met the primary endpoint of freedom from severe vaso-occlusive crisis for at least 12 consecutive months. The mean duration of freedom from vaso-occlusive crisis was 22.4 months, ranging from 14.8 months to 45.5 months. Moreover, 28 of the 29 patients who remained crisis-free at 12 months did not have a further vaso-occlusive crisis throughout the rest of the follow-up period.

Dr. Frangoul noted that results were similar for both adults and adolescents.

Exa-cel also led to a significant increase in freedom from inpatient hospitalizations, with 100% of patients achieving that goal, as well as early and sustained increases in both total and fetal hemoglobin levels, suggesting a “long-term meaningful benefit” from the therapy.

All 44 patients experienced adverse events related to myeloablative conditioning with busulfan, but only 29.5% had events linked to exa-cel. The most common adverse events overall were nausea (70.5%), stomatitis (63.6%), vomiting (56.8%), and febrile neutropenia (54.5%).

In a separate poster presented at ASH, Akshay Sharma, MBBS, of St. Jude Children’s Research Hospital in Memphis, Tennessee, Dr. Frangoul, and colleagues reported that exa-cel also led to better health-related quality of life. 

Patients showed “substantial improvements” in measures of quality of life, which included physical, emotional, social, and functional well-being as well as pain at a 6-month follow-up through year 2.

Typical outcomes studied in most trials are “emergency room visits and hospitalizations but what people may not appreciate as much is how much these patients are dealing with pain and discomfort at home,” Dr. O’Brien said. These recently reported quality-of-life metrics “are so key and really help us understand the impact” of this new therapy.

Dr. O’Brien noted, however, that “patients may be reluctant to undergo” this therapy because of the impact myeloablative conditioning has on fertility. That is why ongoing research on how stem cell transplants can be delivered “without impacting fertility is very important.”

It is “hard to know,” Dr. O’Brien explained, whether exa-cel will be a one-time treatment in practice, as many of the patients “already have end-organ damage from their disease.” 

To that end, Dr. Frangoul noted that patients who complete the current trial can enroll in one that will include 13 years of additional follow-up.

Finally, Dr. O’Brien cautioned, gene therapies such as exa-cel “are only going to apply to a small segment of the population” — patients with the most severe form of the disease. That’s why “it’s important that we still prioritize hydroxyurea [and] multidisciplinary care for patients with sickle cell disease,” she said.

The study was sponsored by Vertex Pharmaceuticals in collaboration with CRISPR Therapeutics. Dr. Frangoul declared relationships with Editas Medicine, Rocket Pharmaceuticals, Jazz Pharmaceuticals, Vertex Pharmaceuticals, CRISPR Therapeutics, Bluebird Bio, and others. Dr. Sharma declared relationships with Vertex Pharmaceuticals, CRISPR Therapeutics, and others. Other authors declare numerous financial relationships.

A version of this article appeared on Medscape.com.

Earlier this month, the U.S. Food and Drug Administration (FDA) approved two gene-editing therapies for patients aged 12 years or older with severe sickle cell disease.

One therapy — exagamglogene autotemcel or exa-cel (Casgevy) — is the first to use CRISPR gene-editing technology, and could “provide a one-time functional cure to patients with sickle cell disease,” said Haydar Frangoul, MD, of The Children’s Hospital at TriStar Centennial, Nashville, Tennessee.

Dr. Frangoul, who presented a recent interim analysis on the therapy at the American Society of Hematology (ASH) annual meeting earlier this month, reported that one infusion of exa-cel prompted rapid increases in total hemoglobin levels and almost completely eliminated a common and painful complication of sickle cell disease that can lead to irreversible organ damage, known as vaso-occlusive crisis.

Overall, the gene therapy led to “a rapid, robust, and durable increase in total hemoglobin to normal or near normal levels,” Dr. Frangoul said.

Exa-cel, from Vertex Pharmaceuticals and CRISPR Therapeutics, is a single-dose infusion containing a patient’s modified cells. First, a patient’s stem cells are harvested and then genetically modified to produce fetal hemoglobin. 

The development of exa-cel was “grounded in human genetics, which show that fetal hemoglobin can substitute for sickle hemoglobin,” Dr. Frangoul explained. Patients receive these edited cells, which then help restore normal hemoglobin production.

The analysis showed that a one-time infusion of exa-cel following myeloablative conditioning prevented vaso-occlusive crisis in all but one patient with severe sickle cell disease. The therapy also prevented inpatient hospitalizations for vaso-occlusive crisis in all patients and led to sustained improvements in quality of life.

The results are “really striking,” said Sarah H. O’Brien, MD, of Nationwide Children’s Hospital in Columbus, Ohio, who was not involved in the research. “The majority of our admissions on the hematology service are our patients with sickle cell. They’re uncomfortable, they’re in pain, they’re missing school, and they’re missing their activities,” which makes these interim findings quite “impactful.”

To examine the impact of exa-cel on vaso-occlusive crisis, the phase 3 trial included individuals aged 12 to 35 years with severe sickle cell disease and a history of at least two vaso-occlusive crises per year over the past 2 years.

Participants underwent cell CD34+ stem cell collection. These cells then underwent gene editing using CRISPR technology, explained Dr. Frangoul.

At the transplant center, patients received myeloablative conditioning chemotherapy with busulfan for 4 days before receiving an exa-cel infusion.

At the data cutoff in June 2023, 44 patients had been enrolled, of whom 30 were available for efficacy analysis. The mean age at screening was 22.1 years, and almost half (46.7%) were female. Prior to study recruitment, patients had a mean of 3.9 vaso-occlusive crises per year and a mean of 2.7 inpatient hospitalizations per year for severe vaso-occlusive crisis.

All but one patient (96.7%) met the primary endpoint of freedom from severe vaso-occlusive crisis for at least 12 consecutive months. The mean duration of freedom from vaso-occlusive crisis was 22.4 months, ranging from 14.8 months to 45.5 months. Moreover, 28 of the 29 patients who remained crisis-free at 12 months did not have a further vaso-occlusive crisis throughout the rest of the follow-up period.

Dr. Frangoul noted that results were similar for both adults and adolescents.

Exa-cel also led to a significant increase in freedom from inpatient hospitalizations, with 100% of patients achieving that goal, as well as early and sustained increases in both total and fetal hemoglobin levels, suggesting a “long-term meaningful benefit” from the therapy.

All 44 patients experienced adverse events related to myeloablative conditioning with busulfan, but only 29.5% had events linked to exa-cel. The most common adverse events overall were nausea (70.5%), stomatitis (63.6%), vomiting (56.8%), and febrile neutropenia (54.5%).

In a separate poster presented at ASH, Akshay Sharma, MBBS, of St. Jude Children’s Research Hospital in Memphis, Tennessee, Dr. Frangoul, and colleagues reported that exa-cel also led to better health-related quality of life. 

Patients showed “substantial improvements” in measures of quality of life, which included physical, emotional, social, and functional well-being as well as pain at a 6-month follow-up through year 2.

Typical outcomes studied in most trials are “emergency room visits and hospitalizations but what people may not appreciate as much is how much these patients are dealing with pain and discomfort at home,” Dr. O’Brien said. These recently reported quality-of-life metrics “are so key and really help us understand the impact” of this new therapy.

Dr. O’Brien noted, however, that “patients may be reluctant to undergo” this therapy because of the impact myeloablative conditioning has on fertility. That is why ongoing research on how stem cell transplants can be delivered “without impacting fertility is very important.”

It is “hard to know,” Dr. O’Brien explained, whether exa-cel will be a one-time treatment in practice, as many of the patients “already have end-organ damage from their disease.” 

To that end, Dr. Frangoul noted that patients who complete the current trial can enroll in one that will include 13 years of additional follow-up.

Finally, Dr. O’Brien cautioned, gene therapies such as exa-cel “are only going to apply to a small segment of the population” — patients with the most severe form of the disease. That’s why “it’s important that we still prioritize hydroxyurea [and] multidisciplinary care for patients with sickle cell disease,” she said.

The study was sponsored by Vertex Pharmaceuticals in collaboration with CRISPR Therapeutics. Dr. Frangoul declared relationships with Editas Medicine, Rocket Pharmaceuticals, Jazz Pharmaceuticals, Vertex Pharmaceuticals, CRISPR Therapeutics, Bluebird Bio, and others. Dr. Sharma declared relationships with Vertex Pharmaceuticals, CRISPR Therapeutics, and others. Other authors declare numerous financial relationships.

A version of this article appeared on Medscape.com.

Earlier this month, the U.S. Food and Drug Administration (FDA) approved two gene-editing therapies for patients aged 12 years or older with severe sickle cell disease.

One therapy — exagamglogene autotemcel or exa-cel (Casgevy) — is the first to use CRISPR gene-editing technology, and could “provide a one-time functional cure to patients with sickle cell disease,” said Haydar Frangoul, MD, of The Children’s Hospital at TriStar Centennial, Nashville, Tennessee.

Dr. Frangoul, who presented a recent interim analysis on the therapy at the American Society of Hematology (ASH) annual meeting earlier this month, reported that one infusion of exa-cel prompted rapid increases in total hemoglobin levels and almost completely eliminated a common and painful complication of sickle cell disease that can lead to irreversible organ damage, known as vaso-occlusive crisis.

Overall, the gene therapy led to “a rapid, robust, and durable increase in total hemoglobin to normal or near normal levels,” Dr. Frangoul said.

Exa-cel, from Vertex Pharmaceuticals and CRISPR Therapeutics, is a single-dose infusion containing a patient’s modified cells. First, a patient’s stem cells are harvested and then genetically modified to produce fetal hemoglobin. 

The development of exa-cel was “grounded in human genetics, which show that fetal hemoglobin can substitute for sickle hemoglobin,” Dr. Frangoul explained. Patients receive these edited cells, which then help restore normal hemoglobin production.

The analysis showed that a one-time infusion of exa-cel following myeloablative conditioning prevented vaso-occlusive crisis in all but one patient with severe sickle cell disease. The therapy also prevented inpatient hospitalizations for vaso-occlusive crisis in all patients and led to sustained improvements in quality of life.

The results are “really striking,” said Sarah H. O’Brien, MD, of Nationwide Children’s Hospital in Columbus, Ohio, who was not involved in the research. “The majority of our admissions on the hematology service are our patients with sickle cell. They’re uncomfortable, they’re in pain, they’re missing school, and they’re missing their activities,” which makes these interim findings quite “impactful.”

To examine the impact of exa-cel on vaso-occlusive crisis, the phase 3 trial included individuals aged 12 to 35 years with severe sickle cell disease and a history of at least two vaso-occlusive crises per year over the past 2 years.

Participants underwent cell CD34+ stem cell collection. These cells then underwent gene editing using CRISPR technology, explained Dr. Frangoul.

At the transplant center, patients received myeloablative conditioning chemotherapy with busulfan for 4 days before receiving an exa-cel infusion.

At the data cutoff in June 2023, 44 patients had been enrolled, of whom 30 were available for efficacy analysis. The mean age at screening was 22.1 years, and almost half (46.7%) were female. Prior to study recruitment, patients had a mean of 3.9 vaso-occlusive crises per year and a mean of 2.7 inpatient hospitalizations per year for severe vaso-occlusive crisis.

All but one patient (96.7%) met the primary endpoint of freedom from severe vaso-occlusive crisis for at least 12 consecutive months. The mean duration of freedom from vaso-occlusive crisis was 22.4 months, ranging from 14.8 months to 45.5 months. Moreover, 28 of the 29 patients who remained crisis-free at 12 months did not have a further vaso-occlusive crisis throughout the rest of the follow-up period.

Dr. Frangoul noted that results were similar for both adults and adolescents.

Exa-cel also led to a significant increase in freedom from inpatient hospitalizations, with 100% of patients achieving that goal, as well as early and sustained increases in both total and fetal hemoglobin levels, suggesting a “long-term meaningful benefit” from the therapy.

All 44 patients experienced adverse events related to myeloablative conditioning with busulfan, but only 29.5% had events linked to exa-cel. The most common adverse events overall were nausea (70.5%), stomatitis (63.6%), vomiting (56.8%), and febrile neutropenia (54.5%).

In a separate poster presented at ASH, Akshay Sharma, MBBS, of St. Jude Children’s Research Hospital in Memphis, Tennessee, Dr. Frangoul, and colleagues reported that exa-cel also led to better health-related quality of life. 

Patients showed “substantial improvements” in measures of quality of life, which included physical, emotional, social, and functional well-being as well as pain at a 6-month follow-up through year 2.

Typical outcomes studied in most trials are “emergency room visits and hospitalizations but what people may not appreciate as much is how much these patients are dealing with pain and discomfort at home,” Dr. O’Brien said. These recently reported quality-of-life metrics “are so key and really help us understand the impact” of this new therapy.

Dr. O’Brien noted, however, that “patients may be reluctant to undergo” this therapy because of the impact myeloablative conditioning has on fertility. That is why ongoing research on how stem cell transplants can be delivered “without impacting fertility is very important.”

It is “hard to know,” Dr. O’Brien explained, whether exa-cel will be a one-time treatment in practice, as many of the patients “already have end-organ damage from their disease.” 

To that end, Dr. Frangoul noted that patients who complete the current trial can enroll in one that will include 13 years of additional follow-up.

Finally, Dr. O’Brien cautioned, gene therapies such as exa-cel “are only going to apply to a small segment of the population” — patients with the most severe form of the disease. That’s why “it’s important that we still prioritize hydroxyurea [and] multidisciplinary care for patients with sickle cell disease,” she said.

The study was sponsored by Vertex Pharmaceuticals in collaboration with CRISPR Therapeutics. Dr. Frangoul declared relationships with Editas Medicine, Rocket Pharmaceuticals, Jazz Pharmaceuticals, Vertex Pharmaceuticals, CRISPR Therapeutics, Bluebird Bio, and others. Dr. Sharma declared relationships with Vertex Pharmaceuticals, CRISPR Therapeutics, and others. Other authors declare numerous financial relationships.

A version of this article appeared on Medscape.com.