An international group of clinicians has proposed time to next treatment (TTNT) as a clinically meaningful endpoint to be applied in future studies of primary cutaneous T-cell lymphoma (CTCL).

Writing in the Open Access journal Cancers, the UK, US and Australian authors said TTNT was a useful surrogate for the duration of clinical benefit.

It is already an accepted endpoint in clinical trials of multiple myeloma and has been used in other haematological and solid cancers, they said.

“TTNT measures the interval from the date of initiation of a treatment to the date of commencement of the next line of therapy, thereby allowing for easy measurement of the period of therapeutic benefit.”

“Furthermore, TTNT offers a better reflection of the patients’ treatment experiences than conventional disease-related endpoints by incorporating the time course of treatment tolerability and patient compliance.”

The authors, including Professor Miles Prince and Associate Professor Christopher McCormack from the Peter MacCallum Cancer Centre, said discordant disease responses in skin, nodes, viscera or blood can limit the usefulness of other endpoints in CTCL.

They reviewed the use of TTNT in published CTCL studies and found it has been validated in at least two – here and here – prospective studies.

“For CTCL patients with intermediate-long clinical courses, multiple therapeutic options, and no clearly defined optimal treatment sequence, TTNT represents a valuable tool to measure and compare the efficacy and durability of therapeutic benefit of established and novel therapies,” they concluded.

Some of the components of a new standardised definition for TTNT included:

• TTNT is measured from the date of initiation (first dose) of treatment to the date of initiation of the next line of therapy.
• The next line of therapy excludes skin-directed therapies such as topical steroids, nbUVB/PUVA or focal radiation where less than 50% of the skin is irradiated.
• Where patients are not fit for active management or decline further anti-CTCL treatment, the next line of treatment commences at withdrawal of active treatment and/or commencement of end of life care
• Short term treatment gaps e.g. treatment withheld for <2 months due to intercurrent illness or relief of toxicities, do not trigger a ‘next line of therapy’
• Pre-planned consolidation /maintenance therapy in a patients with controlled disease does not trigger a TTNT event
• For allogeneic transplant recipients, TTNT is triggered at the start of conditioning therapy.