Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma.

In phase 2 of ZUMA-1, a single-arm, multicenter, registrational trial, axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy demonstrated durable responses at 2 years in patients with refractory large B-cell lymphoma (LBCL). Here, we assessed outcomes in ZUMA-1 after 5 years of follow-up. Eligible adults received lymphodepleting chemotherapy followed by axi-cel (2 × 106 cells per kg). Investigator-assessed response, survival, safety, and pharmacokinetics were assessed in patients who had received treatment. The objective response rate in these 101 patients was 83% (58% complete response rate); with a median follow-up of 63.1 months, responses were ongoing in 31% of patients at data cutoff. Median overall survival (OS) was 25.8 months, and the estimated 5-year OS rate was 42.6%. Disease-specific survival (excluding deaths unrelated to disease progression) estimated at 5 years was 51.0%. No new serious adverse events or deaths related to axi-cel were observed after additional follow-up. Peripheral blood B cells were detectable in all evaluable patients at 3 years with polyclonal B-cell recovery in 91% of patients. Ongoing responses at 60 months were associated with early CAR T-cell expansion. In conclusion, this 5-year follow-up analysis of ZUMA-1 demonstrates sustained overall and disease-specific survival, with no new safety signals in patients with refractory LBCL. Protracted B-cell aplasia was not required for durable responses. These findings support the curative potential of axi-cel in a subset of patients with aggressive B-cell lymphomas. This trial was registered at ClinicalTrials.gov, as #NCT02348216.

An innovative method of retrieval of the broken suction cannula tip during medical termination of pregnancy using a fibrobronchoscope during the coronavirus disease 2019 pandemic.

The breaking of the tip of the 'Karman cannula' inside the uterine cavity while performing suction curettage for missed abortion is an extremely rare phenomenon. Ideally, such foreign bodies should be removed using a hysteroscope under direct vision. In the absence of a hysteroscope, retrieval may be attempted using retrieving forceps either under ultrasonographic guidance or blindly. A 26-year-old female patient presented as a case of missed abortion at 6 weeks of gestation and underwent suction and evacuation. The tip of the cannula broke during the procedure. Multiple attempts were made to retrieve the cannula tip using forceps under ultrasound guidance without success. The patient was planned to be shifted to a higher centre as the hysteroscope was not available at this centre. However, owing to travel restrictions and lockdown imposed for the coronavirus disease 2019 (COVID 2019) pandemic, the patient could not be transferred. An innovative method using the fibre optic bronchoscope was devised by the otorhinolaryngologist and gynaecologist, and the retained impacted cannula was safely removed from the left uterine cornu under vision.

Comparative efficacy of cemiplimab versus other systemic treatments for advanced cutaneous squamous cell carcinoma.

Aim: To estimate the comparative efficacy of cemiplimab, a programmed cell death protein 1 inhibitor, versus EGFR inhibitors, pembrolizumab and platinum-based chemotherapy in terms of overall survival (OS) and progression-free survival. Patients & methods: We performed an indirect treatment comparison of cemiplimab and other available systemic therapies for patients with advanced cutaneous squamous cell carcinoma. Results: Cemiplimab was associated with benefits in OS (hazard ratios range: 0.07-0.52) and progression-free survival (hazard ratios range: 0.30-0.67) versus EGFR inhibitors and pembrolizumab (data from KEYNOTE-629). Cemiplimab was more efficacious versus platinum-based chemotherapy in terms of OS. Conclusion: Cemiplimab may offer improvements in survival for advanced cutaneous squamous cell carcinoma patients compared with existing systemic therapies.

The potential global market size and public health value of an HIV-1 vaccine in a complex global market.

An effective HIV vaccine will be essential for the control of the HIV pandemic. This study evaluated the potential global market size and value of a hypothetical HIV vaccine and considered clade diversity, disease burden, partial prevention of acquisition, impact of a reduction in viral load resulting in a decrease in transmission and delay to treatment, health care system differences regarding access, and HIV screening and vaccination, across all public and private markets. Vaccine product profiles varied from a vaccine that would have no effect on preventing infection to a vaccine that would effectively prevent infection and reduce viral load. High disease burden countries (HDBC; HIV prevalence > or = 1%) were assumed to routinely vaccinate pre-sexually active adolescents (10 years old), whereas low disease burden countries (LDBC; HIV prevalence rate <1%) were assumed to routinely vaccinate higher risk populations only. At steady state, routine vaccination demand for vaccines that would prevent infection only was 22-61 million annual doses with a potential market value of $210 million to $2.7 billion, depending on the vaccine product profile. If one-time catch-up campaigns were included (11-14 years old for HDBC and higher risk groups for LDBC), the additional cumulative approximately 70-237 million doses were needed over a 10-year period with a potential market value of approximately $695 million to $13.4 billion, depending on the vaccine product profile. Market size and value varied across market segments with the majority of the value in high income countries and the majority of the demand in low income countries. However, the value of the potential market in low income countries is still significant with up to $550 million annually for routine vaccination only and up to $1.7 billion for a one-time only catch-up campaign in 11-14 years old. In the most detail to date, this study evaluated market size and value of a potential multi-clade HIV vaccine, accounting for differences in disease burden, product profile and health care complexities. These findings provide donors and suppliers highly credible new data to consider in their continued efforts to develop an HIV-1 vaccine to address the worldwide disease burden.

Understanding the impact of male circumcision interventions on the spread of HIV in southern Africa.

BACKGROUND: Three randomised controlled trials have clearly shown that circumcision of adult men reduces the chance that they acquire HIV infection. However, the potential impact of circumcision programmes--either alone or in combination with other established approaches--is not known and no further field trials are planned. We have used a mathematical model, parameterised using existing trial findings, to understand and predict the impact of circumcision programmes at the population level. FINDINGS: Our results indicate that circumcision will lead to reductions in incidence for women and uncircumcised men, as well as those circumcised, but that even the most effective intervention is unlikely to completely stem the spread of the virus. Without additional interventions, HIV incidence could eventually be reduced by 25-35%, depending on the level of coverage achieved and whether onward transmission from circumcised men is also reduced. However, circumcision interventions can act synergistically with other types of prevention programmes, and if efforts to change behaviour are increased in parallel with the scale-up of circumcision services, then dramatic reductions in HIV incidence could be achieved. In the long-term, this could lead to reduced AIDS deaths and less need for anti-retroviral therapy. Any increases in risk behaviours following circumcision, i.e. 'risk compensation', could offset some of the potential benefit of the intervention, especially for women, but only very large increases would lead to more infections overall. CONCLUSIONS: Circumcision will not be the silver bullet to prevent HIV transmission, but interventions could help to substantially protect men and women from infection, especially in combination with other approaches.

Oral healthcare for elderly: identifying the needs and feasible strategies for service provision.

The aim of the present study was to assess the oral health practices, status and treatment needs of the rural elderly in national capital territory of Delhi. An effort was also made to identify patterns of utilization of dental services and test alternate strategies for service provision. A total of 96 elderly subjects (47 males and 49 females) in 5 rural areas were interviewed and clinically examined using Basic Oral Health Survey criteria of W.H.O. This was followed by a community trial in which the 5 villages were divided into control and test groups. Results of the survey found that both traditional as well as modern oral health practices co-exist in the rural community. Dental services were available to a majority (mostly through private sector), and edentulousness was a condition of primary concern among the elderly as a result of unmet treatment needs for dental caries and periodontal diseases. Age was a variable that was statistically significantly associated with edentulousness (p=0.005). Results of the community trial showed that higher utilization of care can be achieved by providing on-site dental care as compared to referring cases to tertiary care centers. Nevertheless provision of treatment alone is not a suitable policy recommendation since many elderly did not avail care even at on-site community dental health programmes that were operated free of cost. This emphasizes the need of health education over treatment in order to empower the elderly, especially the non-ambulatory patients, to practice prevention and develop favourable attitudes towards accepting prompt treatment at primary health care level.