Bone marrow impairment during early [177Lu]PSMA-617 radioligand therapy: Haematotoxicity or tumour progression?

Abstract

Background The recent phase III VISION-trial confirms the treatment efficacy of radioligand therapy with [177Lu]PSMA-617 (PSMA-RLT) in metastatic castration-resistant prostate cancer (mCRPC). In PSMA-RLT, the relatively low absorbed bone marrow dose allows for multiple therapy cycles with relatively low risk of haematological adverse events (hAE). However, as disease progression itself may be a cause of bone marrow impairment, the aim of this study was to assess potential relations between impairment of haematological status and response to PSMA-RLT. Methods In this retrospective analysis, haematological parameters (HP) of 64 patients with mCRPC were systematically acquired over two cycles (12–16 weeks) of PSMA-RLT from baseline to restaging. Changes in HP were analysed qualitatively (CTCAE 5.0) and quantitatively. The HP changes from baseline were compared to quantitative and qualitative biochemical and imaging response, using PCWG3 and PROMISE criteria. Results All grade 3/4 hAE observed were associated with disseminated or diffuse bone involvement as well as biochemical non-response at restaging. Quantitatively, at baseline, HP inversely correlated with biochemical and volumetric (on PET) tumour burden as well as bone involvement pattern (p ≤ 0.043). Among patients with disseminated or diffuse bone involvement, percentage changes in HP (%HP) at restaging inversely correlated with serological and imaging tumour burden (p ≤ 0.017). Biochemical non-responders showed a significant decrease in %HP (p ≤ 0.001) while HP in biochemical responders remained stable (p ≥ 0.079). Conclusion During early cycles of PSMA-RLT, qualitative and quantitative bone marrow impairment appears to be closely associated with osseous tumour burden as only patients with advanced bone involvement and non-response to therapy exhibited high-grade haematological adverse events, showing a significant decline of haematological parameters. This implies that in patients with advanced mCRPC, non-response to PSMA-RLT may be a major cause of bone marrow impairment during early treatment cycles. German Clinical Trial Register DRKS00013665. Registered 28 December 2017, retrospectively registered (www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013665)

Improving Overall Survival and Quality of Life in Patients with Prostate Cancer and Neuroendocrine Tumors Using 177Lu-iPSMA and 177Lu-DOTATOC: Experience after 905 Treatment Doses

“…The number of 177 Lu-iPSMA doses to be administered in each treatment was determined based on the tumor volume and the tumor standardized uptake value (SUVmax), estimated by 99m Tc-iPSMA SPECT/CT or 68 Ga-iPSMA PET/CT (radiological molecular imaging) [ 10 ]. For example, tumor burden is related to the number of organic systems involved, including previous hematopoietic damage [ 14 ]. Therefore, patients with higher bone tumor burden were selected to receive a maximum of 3 to 4 doses of 177 Lu-iPSMA due to the increased likelihood of myelotoxicity.…”

“…The results were classified according to the origin of the primary tumors [group 1: GEP-NT (n = 53), and group 2: other NTs (n = 28)] and the number of doses administered [group 3: GEP-NT three to four doses (n = 39); and group 4: GEP-NT five to six doses (n = 14)]. The other NET group received three to four doses (n = 28).…”

Dosimetry for targeted radionuclide therapy in routine clinical practice: experts advice vs. clinical evidence

“…Not to mention that grade 3 bone marrow toxicity remains rare [ 17 , 20 , 21 ] except in patients already heavily treated with chemotherapy in whom the capacities of hematopoietic regeneration seemed more limited and who presented more difficulties recovering from myelodysplastic disease [ 22 , 23 ]. Furthermore, regardless of the bone marrow absorbed doses, the non-responding or even progressive disease itself seems to be one, if not the most important, factor for bone marrow impairment [ 24 ].…”