Health Rounds: Cancer immunotherapies may be more effective given earlier in the day

(Reuters) - Some cancer therapies may be more effective when given earlier in the day, aligning treatment with the body's natural rhythms, a Chinese study found, confirming earlier evidence.

Researchers randomly assigned 210 patients with newly diagnosed advanced non-small cell lung cancer to receive four treatments with Merck's Keytruda and Eli Lilly's Tyvyt, either before or after 3 p.m.

In the group that received treatment before 3 p.m., tumors remained under control for a median 11.3 months, whereas they began to progress at a median 5.7 months in patients treated after 3 p.m.

Median overall survival was 28 months with earlier treatment versus 17 months for those who got later infusions, Dr. Yongchang Zhang of Central South University in Changsha and colleagues reported.

After accounting for individual risk factors, the odds of earlier death were 58% lower with earlier-in-the-day treatment, the researchers wrote in Nature Medicine.

The researchers note that circadian rhythms - the 24-hour cycles governing biological processes - are known to influence immune cells. Earlier retrospective studies have reported improvements in the efficacy of immunotherapies like Keytruda and Tyvyt when given earlier in the day.

Larger studies are still needed to confirm the findings, the researchers acknowledged.

Writing in China’s Journal of the National Cancer Center, a separate team reports that earlier peer-reviewed lab studies showed profound impacts of circadian rhythms on tumor growth and immune cell activity during treatment with drugs that work on the immune system like Keytruda, the world's top-selling prescription medicine.

“Circadian regulation is a critical yet underappreciated factor influencing how tumors interact with the immune system,” study leader Dr. Peng Luo of Southern Medical University in Guangzhou said in a statement.

“By aligning immunotherapy with the body’s natural rhythms, we may significantly enhance treatment outcomes.”

Experimental therapy could be boon for transplant recipients

Organ transplant recipients who currently take multiple pills every day might someday be able to substitute a monthly treatment, a small study suggests.

Along with improved convenience, the new treatment might also reduce side effects and prolong survival of the transplanted organ, researchers said in the American Journal of Transplantation.

Standard immunosuppressants can cause diabetes, hypertension, high cholesterol, and side effects such as fatigue, muscle weakness, sexual dysfunction, hair loss, and trouble sleeping.

In a mid-stage study, 23 kidney recipients received infusions of Bristol Myers Squibb's Nulojix and Amgen’s experimental drug dazodalibep monthly for four months.

These drugs disrupt the immune system's attack on the new organ but do not affect non-immune cells the way standard treatment does, according to the report.

Patients also received standard immunosuppressants for the first 28 days.

Two of the first three patients experienced temporary cases of organ rejection. Drug frequency and dosing were revised for the remaining patients, 13 of whom completed the study.

Seven patients withdrew due to acute kidney rejection, side effects, or for unspecified reasons. None of the rejection episodes were due to the harder-to-treat form known as antibody-mediated rejection, the researchers said.

They now intend to test the regimen in a larger pool of kidney recipients.

“We hope that most patients can be spared the toxic effects of immunosuppressants, which would be reserved for those with certain high-risk factors,” study leader Dr. Allan Kirk of Duke University School of Medicine said in a statement.

Keeping a patient alive without lungs

Doctors for the first time have successfully used an artificial lung system to keep alive a patient without lungs for 48 hours.

The patient had influenza that progressed to lung failure, with the infection rapidly destroying his lungs. He needed to have them removed but was too sick to undergo transplant surgery, explained Dr. Ankit Bharat of Northwestern Medicine in Chicago, who led the team caring for the patient.

To remove the lungs without replacing them, two major problems had to be solved, Bharat said.

“Think of the lungs as a giant sponge that the heart pushes blood through," he said. "This sponge acts like a shock absorber. When you remove the lungs, you remove that cushion."

"Suddenly, the right side of the heart is pumping against clamped vessels - like pumping against a brick wall - which causes it to stretch and fail.”

In addition, the right side of the heart pumps blood to the lungs, which in turn send freshly oxygenated blood back to the left side of the heart. If you remove the lungs, the left side of the heart sits idle because no blood is coming to it, the heart muscle shrinks, and the valves stick shut with blood clots.

In the journal Med, Bharat's team describes how their total artificial lung system used tubes, or shunts, to solve both problems.

“Our system is a new design specifically engineered to maintain normal heart physiology without the lungs,” Bharat said.

One day after the destroyed lungs were removed, "his body started to get better because the infection was gone," Bharat said.

Over the next 48 hours, the patient improved enough to undergo a double-lung transplant. More than two years later, he has returned to daily life with excellent lung function.

“Because it was successful... it provides a blueprint for saving others," Bharat said.