Concurrent Mature T-Cell Lymphoma and Myeloma: Is This a Recurrent Association?

Background: We recently observed two patients with mature T-cell lymphoma (MTL) who

developed a rapidly progressing myeloma (MM). As this association has been only

sporadically reported, we carried out a literature search, and 24 more cases, of MTL,

associated with synchronous or metachronous MM, were found. Giving, the clinical

relevance of this under looked association, we felt it was worth to collect and review

existing reports.

Angioimmunoblastic T-cell lymphoma (AITL): Eight patients had advanced stage AITL, a median

age of 74 years (49-80y), and a Male: Female (M:F) ratio of 7:1. One out of six lymphoma samples

analyzed, was EBV+, and in a different case, MM-cells were EBV+. The diagnosis was synchronous

in two cases, AITL preceded MM in five patients with a median interval of eight months (range 8-

18), while in a last patient lymphoma outbreak 7 years after MM. 5/8 subjects (62.5%) had an IgA

paraprotein, the remaining three an IgM, an IgG, and a k ligh-chain. Four patients had plasma-cell

leukemia while two had only cutaneous dissemination of MM. In six AITL patients, in whom the

outcome was reported, the median overall survival, from the diagnosis of the second malignancy,

was of 2 months (range <1-12 months).

Peripheral T-cell Lymphoma (PTCL-NOS): Five patients were retrieved from the literature. The F:M

ratio was 4:1, the median age 63 years (range=48-88). One out of two cases assessed, was EBV+ in rare

lymphoma-cells. In three out of five subjects, the diagnosis of MM, was synchronous, in another lymphoma

it preceded MM of six months and in the latter PTCL was diagnosed three months later. The

paraproteins were: IgA+IgG, IgG, IgM, and L light-chain, and of undetermined subtype in the last

patient. The median OS from diagnosis of both diseases was 1 month (range=<1-6m).

Anaplastic large-cell Lymphoma (ALCL): all the four cases identified were ALK-negative and had a

synchronous MM diagnosis, associated with IgAL, IgGL, IgML, or IgDL paraproteins. The F:M ratio

was 2:2, and the median age 65 years (63-67). Two cases investigated for EBV were both positive

in lymphoma-cells, and in one of these, EBER was integrated also in plasma-cells. In one case MM

cells, analyzed by FISH showed an adverse profile (t14;16 , del17p13). The median OS was 1

month(<1-12).

Adult T-cell type Lymphoma(ATL): only two female patients with ATL associated with a

synchronous MM were retrieved from the literature. In both cases the two malignancies were

associated with a IgAk paraprotein.

Cutaneous T-cell Lymphomas (PCTL): three patients had CD30+ anaplastic T-cell lymphoma (PC-

ALCL), three mycosis fungoides(MF) and one Sezary Syndrome(SS). In three patients lymphoma

was diagnosed 24, 40 and 72 months respectively, before MM, in another three after MM at a time

interval of 12, 40 and 144 months respectively. Only in one case the diagnosis was synchronous. In

four patients, median OS from the time the 2nd malignancies was reported: was 9 months(1-49).

DISCUSSION: As far as we know, this is the first time, a series of patients with concurrent MTL and MM are collected and reviewed. These data may lead to hypothesize, these malignancies, are recurrently associated. In fact, in the majority of systemic MTL the diagnosis of MM was synchronous and in metachronous cases the interval time between MTL and MM was of few months. Noteworthy, and at odds with published series in isolated MM, the most represented paraprotein was an IgA (47%) and in 18% an IgM. The majority of MTL and MM cases were not EBV-related. Noteworthy the median OS of patients with both malignancies was less than two months. Conversely, in most cutaneous lymphoma, the diagnosis of MM was metachronous, with a median time lapse between the two malignancies of 40 (12-144) months. Most cases were IgG MM, with less severe clinical features, than in patients with systemic MTL. Indeed, more data are necessary to confirm the hypothesis MM and MTL are recurrently associated and eventually to ascertain the underlying mechanisms.

Venditti:astellas: Consultancy, Other: invited speaker; servier: Consultancy, Other: invited speaker; jazz: Consultancy, Other: invited speaker, Research Funding; beigene: Consultancy; glycostem: Consultancy; Gilead: Consultancy, Other: invited speaker; Abbvie: Consultancy, Other: invited speaker; AstraZeneca: Consultancy; laboratories Delbert: Consultancy; menarini: Consultancy, Other: invited speaker; pfizer: Consultancy, Other: invited speaker; BMs celgene: Consultancy, Other: invited speaker; Janssen: Consultancy, Other: invited speaker; istituto gentili: Consultancy.