Coexisting Myeloproliferative and Lymphoproliferative Neoplasms: A European Multicenter Retrospective Study

The coexistence of myeloproliferative neoplasms (MPN) and lymphoid neoplasms (LN) is a rare finding. However, population-based studies have demonstrated that patients with MPN have approximately a 3-fold higher risk of developing an LPN than the normal population.

In this collaborative study among European centers, we retrospectively collected clinical data on adult patients with a concomitant philadelphia negative MPN and LPN diagnosis (dx), according to WHO criteria. This project was approved by the CEI/CEIm HUGCDN, ref. 2020-280-1. The study aimed to advance our understanding of the mixed MPN/LPN syndromes.

We collected data on 149 patients, of whom 81 were male (54.4%). For the patient series, 50% received an MPN dx first (median age at dx 61 years) then LN, 29.6% received an LN dx first (median age at dx 63.5 years) then MPN, while 20.4% had a concomitant dx, this is both neoplasias diagnosed in the same year (median age at dx 66 years). The most frequent LPN dx was chronic lymphocytic leukemia (CLL, 22.8%); the most frequent MPN dx was essential thrombocythemia (ET, 49.6%). There was no association between the type of MPN and a specific LPN except that there was no coexistence of multiple myeloma and PMF. Coexisting neoplasms with the highest incidence were CLL-ET (11.2%, 16/143), with no differences observed between the order of diagnosis (Table 1A). A family history of MPN or LPN was reported for 8.7% of patients.

The distribution of lymphoid neoplasms was different according to the first diagnosis. Thus when LN preceded MPN, the LN were mainly indolent. However if LN diagnosis occurred after, there was a similar distribution between multiple myeloma, high grade B cell lymphomas, CLL and others (Table 1B). We also observed that multiple myeloma usually develops after MPN diagnosis (66.7% in MPN-first vs. 4.8% if LP-first). Similarly, the distribution of MPN was also influenced by the first diagnosis as PV and ET were more common in MPN-first while PMF was uncommon (p=0.001, Table 1C).

Mutated MPN driver genes were JAK2 for 74.5% (n=111, all V617F) of the cases and CALR for 8.7% (n=13); 8.7% of patients were triple negative (n=13). The average time to LPN diagnosis after an initial MPN diagnosis was 8,8 years, while the average time to MPN diagnosis after an initial LPN diagnosis was 10,6 years. In two cases, the diagnosis of the second neoplasm developed was 29 years after.

Overall survival was worse for MPN-first or concomitant diagnosis (p=0.044, Figure 1). This result was independent of patient age and sex, and remained significant if considering separately only patients with PV and marginally with PMF (p=0.036 and p=0.069). We believe this could be due to a delay in the MPN diagnosis, especially in PV, since they are commonly diagnosed after a thrombotic event.

We also studied the timing of the second neoplasia in MPN-first vs. LN-first patients and although MPN-first showed shorter time-at-risk, the difference was not statistically significant (Log Rank test, p=0.128)

A total of 9 patients with a dx of MPN-first received JAK inhibitor treatment (ruxolitinib). Of these, 2 developed LPN after treatment (22.2%), after 1.0 and 3.3 years of treatment.

A total of 38 patients (25.5%) developed a third (non-hematological) neoplasm. No association was found between MPN-first (p=0.254) or LPN-first (p=0.427) and the development of a third (non-hematological) neoplasm. Nor were associations found between hypertension, diabetes, smoking, cholesterol, or obesity with MPN-first or LPN-first.

CONCLUSION

In patients with concomitant myeloproliferative and lymphoid neoplasms there was no association between the type of MPN and a specific LPN yet there was no coexistence of multiple myeloma and PMF. PMF was infrequent as first diagnosis, meaning that it mainly debuted with or after LN diagnosis. ET with CLL was the most frequent MPN-LPN. The worse survival associated with MPN-first may indicate that efforts should be made for earlier detection of MPN. Interestingly, 8.7% of patients had a family history of MPN or LPN. Moreover, almost 26% developed a third neoplasm, indicating that these patients may have a higher predisposition. The reasons why patients with MPN are at higher risk of developing an LPN, or vice versa, are yet to be elucidated, although they may be multiple and the result of a combination of factors, among which there are suggestions of a genetic predisposition.

Fiallo Suarez:ABBVIE: Other: Speakers; AstraZeneca Farmacéutica Spain: Other: Speakers. Stuckey:Novartis: Other: Speakers. Bilbao:Astellas: Other: Speakers. Lemes Castellano:Bristol: Speakers Bureau; Alexion: Speakers Bureau. Ianotto:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Ferrer Marin:Incyte: Research Funding. Gasior Kabat:Novartis: Other: Advisory Board , Speakers Bureau; Eusa Pharma: Speakers Bureau; Brystol Myers Squibb: Other: Advisory Board . Sobas:Celgene/BMS: Honoraria; Novartis: Honoraria. Fox:Sierra Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees. Vallansot:Incyte: Consultancy. Gómez-Casares:Novartis: Speakers Bureau; Pfizer: Speakers Bureau; BMS: Speakers Bureau.