9 replies to this topic

[ta5]

The before-and-after images below would be almost unbelievable if it wasn't in such a respected journal. 

 

JAMA Dermatol. 2017 Jul 12.

Hair Repigmentation During Immunotherapy Treatment With an Anti-Programmed Cell Death 1 and Anti-Programmed Cell Death Ligand 1 Agent for Lung Cancer.

Rivera N1, Boada A1, Bielsa MI1, Fernández-Figueras MT2, Carcereny E3, Moran MT3, Ferrándiz C1.

IMPORTANCE: New targeted therapies for cancer have been released in recent years, opening new horizons in the treatment of patients with cancer. However, their related adverse events (AE) are not fully characterized. Hair repigmentation (HR) is a nondescribed effect secondary to anti-programmed cell death 1 (anti-PD-1) and anti-programmed cell death ligand 1 (anti-PD-L1 ) therapy for treatment of lung cancer (LC), in opposition to the vitiligo reactions that develop during melanoma treatment.

OBJECTIVE: To describe a new adverse event occurring during anti-PD-1/anti-PD-L1 therapy for LC.

DESIGN, SETTING, AND PARTICIPANTS: A case series from a descriptive observation of 14 patients with HR after anti-PD-1/anti-PD-L1 treatment, recruited between September and December, 2016, who were followed up to detect whether they developed cutaneous AE at the time HR was detected. The patients had all been treated in the dermatology department at Hospital Universitari Germans Trias i Pujol, Badalona, Spain.

MAIN OUTCOMES AND MEASURES: Clinical observation of HR during anti-PD-1/anti-PD-L1 therapy for LC, proved by comparing old pictures provided by the patients and recent pictures taken during the follow-up.

RESULTS: Fourteen patients (13 men and 1 woman; mean age, 64.9 years) receiving anti-PD-1 or anti-PD-L1 therapy for non-small-cell lung cancer (NSCLC) presented hair repigmentation during follow-up. This hair repigmentation consisted in a diffuse darkening of the hair in 13 of 14 patients, or in black patches between white hairs in 1. Thirteen of 14 patients presented a good clinical response to the treatment, with at least stable disease, and only 1 had to stop the therapy after only 4 cycles of treatment owing to a life-threatening progression of the disease.

CONCLUSIONS AND RELEVANCE: We present to our knowledge the first report of hair repigmentation owing to anti-PD-1/anti-PD-L1 therapy for lung cancer in a series of 14 patients. Hair repigmentation may be a good response marker in patients receiving anti-PD1/anti-PD-L1 therapy for LC.

PMID: 28700789

 

 

 

[Nate-2004]

So how do we get our hands on nivolumab, pembrolizumab and MPDL-3280A?

[Advocatus Diaboli]

Does anyone here have access to the complete journal article? I'd like to know when the anti-PD-1 and anti-PD-L1 treatments were given to the patients who were described in the abstract as having been "recruited between September and December, 2016.". Does the recruitment time mean that the treatment was administered during that time frame?

 

Knowing the time of treatment would be helpful in understanding if the hair repigmentation (regrowth implied) shown in the photos above (post #1) is consistent with average scalp-hair regrowth rates of about 0.3 to 0.4 mm/day. Or, about 0.9 to 1.2 cm for a 30-day month. How long does their hair look to you?

 

The journal article was published in 2017 Jul 12. The median time from submission to acceptance is 18 days, and 33 days from acceptance to publication--for a total of 51 days from submission to publication. Which if this article is typical it would have been submitted in mid May or so. The time between September 2016 and May 2017 is on the order of 8 months. The article may have been submitted to colleagues prior to submission for publication, which means that it may have been available in some form prior to May 2017.

 

So, is the hair depicted in the photos consistent with changes that might occur in what could be a time period as short as 5 months (using mid December for treatment and mid May for journal submission)? That's why I want to know the time of treatment.

Edited by Advocatus Diaboli, 13 September 2017 - 07:05 PM.

[ta5]

You can find most full articles by searching on sci-hub.io.

http://sci-hub.io/10...matol.2017.2106

[Advocatus Diaboli]

Thanks, ta5, for the link. The information I wanted to find wasn't in the article.

 

It did say "All the patients that presented HR remain in treatment with a partial response or stable disease (SD) except 1, who suspended the treatment after 4 cycles owing to progression of the disease (PD) and finally died. Clinical details are summarized in the Table." (HR--hair repigmentation.).

 

In the "Table" it lists the number of "sessions" with the drugs. The number of sessions ranged from 4 to 38. The starting date of the first session and the time interval between sessions isn't given. The dates for the photos aren't given.

 

All in all, it seems like a pretty low standard for a journal such as JAMA to accept such a poorly documented article.

[ta5]

Here's a new case report on brentuximab that references the study above. The hair color in this individual went from all-white to salt-and-pepper.

 

JAAD Case Rep. 2017 Nov 8;3(6):563-565. doi: 10.1016/j.jdcr.2017.09.027. eCollection 2017 Nov.

Hair repigmentation associated with the use of brentuximab.

Penzi LR1, Manatis-Lornell A1, Saavedra A2, Fisher D1,3, Senna MM1,3.

PMID: 29159251

 

 

[kench]

From the JAAD Case report, on mechanism:

 

The mechanism by which these medications cause hair repigmentation is also uncertain. Many reports of medication-induced hair repigmentation concur that these drugs inhibit negative regulators of melanogenesis, such as proinflammatory cytokines tumor necrosis factor (TNF)-α, transforming growth factor-β, interleukin (IL)-1, and IL-6.5, 6, 7, 8 As discussed, CD30 is the key target of brentuximab. CD30 is a member of the TNF receptor family, and it exhibits pleiotropic biologic functions. Antibodies like brentuximab that target CD30 have both agonistic and antagonistic signaling functions.11 CD30 signaling leads to activation of the nuclear factor-κB pathway, which promotes production of proinflammatory cytokines, including IL-6 and TNF- α.12 Specifically, through nuclear factor-κB activation, TNF-α downregulates tyrosinase gene expression, which diminishes the pigmentation pathway in vitro.12 Although tyrosinase expression is not reported to modulate hair graying and might alternatively modulate pigmentation switching between pheomelanin and eumelanin, it is possible that this might contribute to the hair repigmentation seen in individual patients, as described here.

 

Maybe this would only work on a few individuals.

 

[joelcairo]

Interesting but it could be that these patients turned grey from some systemic effect of the lung cancer in the first place.

[ta5]

Here's a different drug that works on IL-17:

 

JAAD Case Rep. 2018 May 7;4(5):486-488.

Repigmentation and new growth of hairs after anti-interleukin-17 therapy with secukinumab for psoriasis

Rongioletti F1, Mugheddu C1, Murgia S1.

PMID: 29984292

 

[joesixpack]

So how do we get our hands on nivolumab, pembrolizumab and MPDL-3280A?

The bottom line - silence.