Immunotherapy Did Not Worsen LEMS in Patient With Lung Cancer

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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small cell lung cancer | Lambert-Eaton News | immune checkpoint inhibitor | Illustration of lungs

A patient with extensive-stage small cell lung cancer and Lambert-Eaton myasthenic syndrome (LEMS) saw a marked decrease in his lung tumors following treatment with a combination of an immune checkpoint inhibitor and chemotherapy — all while having no LEMS flare-ups.

That finding from a recent case report, according to the authors, supports the benefits of immune checkpoint inhibitors for treating cancer patients without the risk of worsening LEMS symptoms.

The report, “An extensive-stage small-cell lung cancer case with preexisting Lambert-Eaton myasthenic syndrome successfully treated with an immune checkpoint inhibitor” was published in the journal Clinical Lung Cancer.

The majority of LEMS cases are associated with cancer, particularly an aggressive type of lung cancer called small cell lung cancer (SCLC).

Patients with extensive-stage SCLC (ES-SCLC) — an advanced stage of SCLC in which tumor cells have spread across the lungs and to other tissues and organs — have been reported to benefit from first-line treatment with a combination of chemotherapy and immune checkpoint inhibitors.

Immune checkpoint inhibitors harness the body’s immune response to fight against cancer by blocking pathways that cancer cells use to avoid being targeted and destroyed by the immune system.

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Tecentriq (atezolizumab), developed by Genentech, a Roche subsidiary, is a type of immune checkpoint inhibitor. It is designed to bind to PD-L1 — a substance produced by cancer cells — and prevent it from interacting with its receptor, PD-1, which can be found on the surface of immune cells. By doing so, the medication effectively blocks a signaling cascade that often is hijacked by cancer cells to dampen the body’s immune responses.

Checkpoint inhibitors like Tecentriq are widely used in cancer therapeutics to reactivate the immune system to attack tumors. However, cancer patients with underlying autoimmune diseases, such as LEMS, have been excluded from trials testing these medications out of concerns it might exacerbate their symptoms.

In this report, authors described the case of a 56-year-old man referred to the Matsusaka Municipal Hospital, in Japan, for suspicion of lung cancer. His symptoms included fatigue when walking, difficulty getting up for weeks, and spitting of blood coming from the airways.

PET/CT scans using a labeled sugar molecule to detect tumor areas confirmed the presence of a tumor mass in his left lung measuring 7.5 cm in diameter. Scans also revealed enlargement of lymph nodes in the mediastinum — a space between both lungs that harbors nerves, blood vessels, and lymph nodes.

After further analysis of a tumor biopsy, he was diagnosed with SCLC. An MRI scan of the brain showed no spreading (metastasis) of tumor cells.

Further clinical evaluation revealed the patient also had LEMS, which was confirmed by the presence of autoantibodies targeting a protein called voltage-gated calcium channel (VGCC) and muscle weakness, primarily in his feet.

The patient was informed of the risk of being treated with a combination of chemotherapy and an immune checkpoint inhibitor, and agreed to receive treatment. He was given two chemotherapy agents — carboplatin and etoposide — in combination with Tecentriq.

After two courses of treatment, CT scans showed a marked decrease in the size of his tumors. Also, his muscle weakness and waddling gait eased, even though he was not receiving any additional treatment specifically for LEMS.

He no longer coughed up blood and regained the ability to climb stairs and conduct his normal daily life without any difficulty. After five months, however, cancer progressed and he has was given a second-line chemotherapy round. His LEMS has been stable over this whole period of time.

“This is the first report about an ES-SCLC patient complicated with LEMS successfully treated by [immune checkpoint inhibitor] plus chemotherapy without a flare-up of LEMS,” the authors wrote.

“[Immune checkpoint inhibitors] in combination with platinum doublet therapy may be a treatment option for ES-SCLC patients complicated with LEMS,” they concluded.